SENSATION I SensorY PERCEPTION...SENSATION I ... 1 SensorY ProCeSSES PERCEPTION I T Psychophysics I...
Transcript of SENSATION I SensorY PERCEPTION...SENSATION I ... 1 SensorY ProCeSSES PERCEPTION I T Psychophysics I...
SENSATION I
1 SensorY ProCeSSESPERCEPTION
I T
Psychophysics
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Thresholds bull absolure bull difference
I Dark adaorarion
Purkinje Shih Juiiouoness contours
Approaches and Issues
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J
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Perceprual organizaoon
I liCiorheories ()f sensorv procesmiddoteuros
I DeorM
t monocuiar t binccuiar
Tieones or VISion bull rncromatic bull opponenr-process
I IPerceprual
constanCIes ize shaoe
color brighrness
I Perceprion or
mocion Illusions
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Theories or heario2 bull piace bull rrequenc
I Theories or sinell
i-ennings Smell Prism
t Theories of caste
Gesialt ~I____________~ rour icste qualicies
T-ieories or palO Spinal-Gare T-eory
T Gestalt iaws
Figure and ground
uuroduCtioll to Pvcboloav 01 Dr i1)raLIIlf 11 f shy
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Lecture Diagam of Sensory Processes
SENSORY PROCESSES
Optic mechanism
Auditory mechanism
Olfactory mechanism f
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IGustatory mechanism I
ICutaneous mechanisms I
I J
Recepcors Transduction
Retina bull rods bull cones
Organ or Coni
I Olfactcry- epithelium
Tasre cells Taste buds
Skin recepcors
1---11(Kinesthetic mechanism
IIVestibular mechanism
J
)
Visual acuiry Color blincness I l Lateral inhibitionJ
Piech and loudness t---til LocacionI
H t I
Free neJe endings Paradoxical cold
Heating IOS5I
I Pheromones
lensrrual synch rony I
I Tase blindness Taste aversionl
ltAcupunctUreI and more Relative temperaturel
4 JOints renoons t---- Internal reeaback and muscles)
Semicircular
canals J
I Tabes dorsalis
i Marion sickness
l Verti20
Centrifugal force
Referred painr-----1( All receptor r----tl~ Chronic painPain mechanisms ~~ems Acute pain
Introduction to Pdlol~ O1 Dr R~aJya M KiD
SENSATION AND PERCEPTION CONCEPT MAP
Sensation
N N
Depth Perception
cues
Environmenta Stimulation Transduction Sensation Perception
~ -- ~ - ~ light Waves I Nerve Impulses
IntrodMction to Psychology 201 Dr Roslllyn M King
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Introduction to Psychology 201 Dr Rosalyn M King
Sensation
What is a sense What is sensation What is the difference between sensation and perception Develop a demonstration of how our sensory processes work and how perception kicks in
Ov What are the five primary senses with definition How does information from your senses get to your brain
o 1 What ispsychophysics Absolute thresholds can be amazingly low what are examples ofshystimuli at the absolute threshold for the five primary senses
o Define and describe sensitivity to stimuli and the signal detection theory Provide examples of the theory in every day life
o Define and describe Webers law and just-noticeable difference (JND) How can you judge the differences between s~imuli
o How would you describe vision What is required for vision Define and describe the accessory structures of the eye including the cornea pupil iris and lens Define the work of the retina and explain how accommodation affects the image on the retina
O Define photoreceptors rods and cones Describe how these structures are involved in transduction and dark adaptation Also describe how cones are involved in hue saturation and brightness
o Describe the path that visul information follows on its way to the brain including the roles of the optic nerve optic chiasm primary visual cortex and feature detectors What creates the blind spot
o Describe the tWo major theories of color vision
o Describe color blindness and its types What do color blind people see l o What are some visual disorders and diseases
o Describe the process ofcoding auditory information What structures of the ear are I involved Define each critical part 0 bull bull
o How do sound waves reach the brain I
--__----_ _---------_ ~-----~----
o Describe the theories of hearing pitch and how we locate sounds
o Describe the nature and causes of hearing loss and describe the effects of noise on hearing and behavior What types of hearing and deafness problems currently exist What is the cochlear implant and what does it do c
o Describe our sense of smell (olfaction) and our sense of taste (gustation) Describe the relationship among taste smell and flavor~ Why does food taste so bland when I have a cold Is there a relationship between smell and memory Between smell and depression Between smell and illness Which is greater- smell or taste
o Describe the transduction process in the olfactory system Discuss the path that olfactory information follows to the brain
o What are pheromones Describe taste buds
o Describe the somatosensory systems which are spread throughout the body Describe the transduction process in the skin senses including touch pain and temperature What does the sense of touch provide
o What is kinesthesia and the vestibular sense What do they provide
o Describe the gate control theory of pain What are the bodys natural analgesics
o Discuss the effects ofsensory restriction
mtToductioa 10 Psycbl)log~ 201 Dr R()lIal~n ~[ Kln~
StJ)tlRY NOTES ON SENSATION (HAI~1)OUT)
Overview of the Humaa Senses
KiDelthia The sense UuglvtZ us information about the location of our body parts and allow our nOVen1elt
Vetibular Setlc Our SclSe ofbalance Viud SenciE ves) Our visual C3ll1cra or window of the world Sight for most pcoplc is be nos imPOrtlllt way of gathering imormation about the world Hurm (Audition) Is feing1t a distance Iniorms us of pressure cbanges in the world illat 7l1y talce place many meters away Physical movement is the stimulus for heariDg Tutc(Gustat1og) ActS as1 gatciceper ro the digestive system by providiDg imormaticn about the substance that may or may not be ingested SweD (Olfaction) Functioos as a distancc sense Provides information about chemic31s suspencied in the air Warns of impending danger as when we sniff escaping gas Plays a role in identifying other pcsoos Touch (Skin Scn~es) Pressure warmth C()ld and pain Enables us to detect what is acijacent to our bodies
Buic Concepts in Sensation
Senorv ReceptOr responsible tor coding iDIormatioo by converting or tansducng raw physicd energy into neurti impulses wbich are then interpreted by our ccnn nervous system T randuction the tramlation of physical energy into electrical signal Sonsorv Deprivation Ii condition mwhich m organism is deprived ot sensory stimulation P3vchophvsio the study of the reiatiooship between the physical narure of stimuli and a persalls sensory rczpooses to lhen
Absolute Threshold det=mining the smallest magnitllde of a stimulus that em be reliably discriminaIed from no stimulus at all 50 pcrccnt ofthc time Sifai-Detection Theorv amp thcory that addresses the role of psyehologica(and other factorS such as costS and benefits) in our ability to identify stimuli D~iding whether we have detected a given stimulus Having [0 rely on p~ decisioo criteria Sennrv Adapt2tioD the reductioo or disappearance ofsensory responsiveness that occurs when stimulation is unchanging or repetitious Difference Threshold or Just NoticubJe Difference (JNl) the minimum difference in intensity that a stimulus em be discriminated Weber Law amp law swing that the smallest detectable diffirence (JND) for myintlnsity of a stimulus is a coostant function of the intcosity of the stimulus This coostanl VariCl tOr C3Ch of the sensory sysums
Vision P311S o(tbe EYe Cornea rUlspannt shield that COVe3 the front of the tye
Lens focuses Iiyenht rays iaIling on the retina Bemis incoming light waves into oarrow rays Pupil opening in the center ofthe iris that helps regulacc the amount of light passing into the reU chamber of the eye Iris Controls the amoUllt ofliglll that cntCS the Ite Retina Is the neural tissue lining the inside back surlacc of the ey~ it absorbs light procsscs images and sends visual intomlauoo to the brain The brains envoy in the eye Contains the Rods aad Canes JaiIling black and white and color vision Optic Nerve a bundle oineunl fibes that eat out the back oithe Ie Cmy oeural imOnnaUon to the brain
Viual Disorder of the Retina Blind Spou occur due [0 a hole in the retinas optic disk You cmnot see the part of he image that falls cn tt Nursightedness fMyoDiah the inability to see objectS far away The eeball is too long so that light from distallt objects focus in front of the retina Farsightedness rHVlJernpia) inability to see objects close up The efebailis too short LigiJt focusC$ on l
lOint bchmd the retina
Page Two) S ummary-SelltioD
C1taracu 311 opague film mat grows over the lens Glaucoma degeneration of the opuc nerve caused by a pressUre buildup withio the yebail due to biockages thaI meet the drainage of the 3CqUeoUS humor Other Visual Disorders Diabetic retinopathy macular degeneration deached reMa
Viual Receptors Rods and Cone Rods 3l1d cones are the pilotorecepton in the reuna rllCY contam chemicals thaI absorb ligbt waves Rods middotAre specialized visual receptors that playa leey role in night vision and periphera vision middotOperate at low light intClSiti= and lead to achromatic (colorless) SClSations -Transmit sensations oilight and darlc only
-You depend on rods for visioll in dim light middotRods cm see only shades of black white and gray -Rods oumumbercones by about 120 million to 7 million -Rods contam lightscnsitive chemical Cllled Rhodopin a necessary clecicd to make Vitamin A A deficiency in both rcsults in night blindneSl Cone middotPlay in key role in daylight vision color vision and fine detail -Conccalrltcti most heavily in the ccntcr of the retina in an area called the fovea -Conuins J chemicals called Iodopins whicplusmn1 are necessary for color vision
Dark Adapration is the process of adapting from bright light to dim light Lizht Adaptation is the process of adapting from darlc to light
Theories ot Color Vision Trichromatic Theo Discovcnd thaI there are J primary colors blue green and red which can be misxcd to form aU other colors Proposes that the human eye has 3 types of receptors with diffmning sensitivities to diifcnnt wavelengths Our ability to peneive a secmingly unlimited array ofcolon results from thejoint action of the tree rcceptor types Our perception of ail colors are plOduced tbrcUyenh comobinations of activity by these 3 types of receptors
People who see a fWl range ofcolorr are ctlled rrich romatJ becmsc they register all J color clwmels Dichromau have only 2 color channels Monochromats are completely blind to diffcrexs in color
The Opponent-Process Theon The theory that color vision is made possible by 3 types of cones some of which respond to red or gnen Jight some to blue or yellow and some only to the intensity of light This theory suggestS thaI above the aeunJ level of the ntina we possess six kinds of cells that playa role in sensatioQS ofcolor Twe of these handle red and green 0= is stimulated by red light and inhibited by green light wberess the other is stimulated by green light and moiled by red IigilL This is why it is C3Iled an opponent-proc=s Two additional cells handle yellow and blue oae is stimulated by yellow light and inhibited by blue while the other shows the opposite pamm The remaining two rypes handle black and white qaU1 in m opponcm process llWlIler
HEARING -The process funcrion or power ofperceiving sound The stimuli for heuing or audition are sound waves - High and low sounds cm be distinguised by their pitch -The e3lis the structure through which we percive sound P3rtS oiilie eu include outer (visible part-funnes soundwaves into e3r cma1 that strikes the eItdrum) middle (includes the hammer anvil stirrup and OVU window) and inner (contains the auditory receptorsmiddot the cochlea and basilar mcnbrane)
Theories otHearinlo Pitch Ptace TheG f)t Pitch The piech of a sound is determined by the plac slong the basilarlIlCnbrane that vibraus in nsponse to it The bigher the pitch of soum the closer the nsponsive IlelfOQS lie to the oval window
Page Three) Summary-SensaciOD
Frequency Theon of Pitch Pilch perception depends on the stimulation of neural impulses that match the frequency of the sound waves DupUdty Theon Pitch perception depends both on tbeplacc and frequency oineural response
TYpa ot Hearinl Problemll
Conduetfon De_fnen Hearing loss caU$Cd by wax or injwy Sellllo[-Neural Deafne Loss caused by injwy to the hair cells or audjtory nerves Damage IS irreversible Stimulation DeafDen Deafness due to exposure to sounds that are exccsslvely loud Centra Dearness Caused by disease and tumors in the audilOry pathways and cortex of the brain Untreatablc
Cochlear Implant An artificial hearing device implanted in the skull Motion Slslmell Involves strlCtuns in the inner ear - the vestibular organs
Ioucb A number of diffennt skin sensatioas After the free nerve endings convert pressure warmth cold and paiD into nerve impulses these impulses ultimately reach the somatosensory area of the cortex At this point you experience the sensation of touch
lm A sigual that somcthiDg is wrong in the body Eadorphins act to reduce pain Gat Control Theory otPaln Involves the brain providing insttuctions to neurons to reie3Se endorphins and block pain in the body
Tate Tute is I chemical sense that responds to the chemical stl1ICtUre of substances Four basic tastes sweet salty sour bitta
SmeU The seme ofsmell is ten thousand times more sensitive than taste The firing ofneurons transmits information about odors to the brain via the olfactory bulb
Popular Studies re olfaction
Menstrual Svnchrony Psychologisc Martha McClintock monitored the menstrual cycles of 13Swomen and found that the cycles offtiends and roommates converged due to their spending time in close quarters
Pbernmones Produced by other members of the species and detected through the sense of smell Example animaLs marking territory Scents induce mating behavior
Dr ROSMYII M XlIIK ntrotblcdoll to Psycllology Article 8
F 7 cmr g RB
Sensational Thne-ups Fifteen ways to improve your vision hearing taste and sense of smell
SID KIRCHHEIMER
Are people around you mumbling more often these days Does food seem to need an extra splash of Tabasco to please the palate Would the newspaper be easier to read
if your arms were just a few feet longer and the print a bit bigger Welcome to the club By the time we hit middle age most of
us suffer from some decline of the senses But dont despair There are ways to protect-and even improve-your ability to see hear smell and taste all of lifes offerings Experts we conshysulted recommend the following senses-sharpening middotstrategies
Sight Only reading glasses or other special eyewear can foil the common cause of weakened vision presbyopia the so-called aging eyes that result when the lens of the eye loses its flexishybility making it harder to focus clearly on close objects But you can take measures to stave off some of the leading causes of age-related blindness See if these work for you
Pop five a day A National Eye Institute study shows that one of the best ways to arrest macular degeneration is by following a simple five-pill supplement regimen daily doses of500 mg of vishytamin C 400 intemational units of vitamin E 15 mg of beta carshyotene 80 mg of zinc oxide and 2 mg of cupric oxide You really need to take these in supplement form because there is no way you could get these amounts from food alone says National Eye mstitute researcher Emily Chew MD
Loosenup A study in the British Journal of Ophthalmology finds that a tight necktie may increase risk of glaucoma by conshystricting neck veins boosting fluid pressure inside the eyes to dangerous levels No one says you have to strangle yourself says study author Robert Ritch MD of the New York Eye and Ear Infirmary If you cant get your finger in between your neck and your collar easily its too tight
Keep your specs on The mainstay material in prescription eyewear-polycarbonate lenses-helps block harmful ultravishyolet light a key cause of cataracts says ophthalmologist Wilshyliam Uoyd MD of UC Davis Medical Center So keep your glasses on whenever youre outdoors (or don prescription sunshyglasses) And if youre 2020 look for nonprescription sunshy
glasses at the drugstore or mall that are labeled to protect against both UV A and UVB rays
Plow Into power plants Some of the disease-protecting chemicals naturaIly found in fruits and vegetables also shield these plants from UV rays and other environmental pollutants that can damage your vision While most types of produce are beneficial peas peppers and green leafy vegetables such as kale romaine lettuce and spinach stand out because theyre rich in lutein and other key vision-protecting nutrients
Get an early start Eye-harming environmental pollutantsshysmog in plain Englisb-are at their lowest levels early in the day To limit your exposure to toxins in the air Lloyd suggests doing yani work exercise and other outdoor activities early in the moming
Hearing While illness injury overuse of certain drugs and genetics can all lead to hearing loss the primary reason most aging Amerishycans go deaf is their past exposure to noise With every noise that is loud or long enough some of the 6000 or so tiny hairs inside each ear that allow sound waves to be heard are permashynently damaged causing a gradual hearing loss that becomes noticeable in middle age and beyond Some sound advice
Plug em Wearing ear protection is the obvious way to protect these sensitive hair ceUs but you dont have to look like an aipOl1 bagshygage handlerwhile doing it Small foam plugs that discreetly fit in your ear may actually be better than the bulky padded earmuff types says David Nielsen MD of the American Academy of OtolaryngologyshyHead and Neck Surgery These plugs reduce noise by about 20 decishybels compared with the 15-decibel protection you get from more exshypensive padded earmuffs Plus the plugs are cooler he points out
Work out In silence Regular exercise keeps hearing sharp by improving or maintaining good blood flow to the inner ear But during exercise when more blood is feeding muscles less may get to nerves that control hearing making them more vulnerable to noise-caused damage Some studies indicate that loud music or noise heard during exercise may be more damaging than noise heard at the same volumes when youre sedentary Researchers are not unanishymous about this but unless you need to listen to loud music while you exe~~ you probably shouldnt says Nielsen
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ANNUAL EDIT10NS
Spark Your Sixth Sense
Just for fun we asked leading experts what can be done to maintain or enhance the sixth sense -abilities such as ESP telepathy and clairvoyance It turns out psychic abilities may actually benefit from aging Conditions that are more conducive for psychic experiences seem to ocshycur more readily in older people than in younger ones says researcher Emily Williams Kelly PhD of the Unishyversity of Virginias division of personality studies which studies psychic phenomena How better to get in touch with the other side Consider the following
bull Use the quiet When the house is absent of yelling kids blaring music and other immediate distractions youre more likely to be able to focus on the beyond These events seem to occur more readily in those who have them with quiet solitude and meditation says Kelly
bull Watch for signs People who are extroverted and open to the idea of having these experiences are more likely to show ESP abilities says Kelly And their glass is half fullft attitude includes taking clues from everyday events middotSigns are everywhere adds Lisa Nash a clairvoyant and online psychic reader at Global Psychic Inc Pay attention to what you see while you are driving It may be an indication of whats in your lifes path A dead deer on the side of the road might indicate that you are neglecting your inner power that comes from gentleness
bull Eat for illumination Nash says many psychics eat healthfully avoiding alcohol and drugs as well as
caffeine sugar and processed foods in order to maintain mental focus and clarity Meanwhile recent research shows that one of the omega-3 fatty acids found in heart-healthy fish such as salmon and mackerel can prevent age-related damage to a part of the brain where cells responsible for learning and memory communicate with one another -SK
Dont be a blowhard Strenuous nose blowing can cause temporary or pennanent hearing loss by rupturing the delicate structures inside the eardrum To relieve nasal congestion adshyvises Nielsen gently blow one nostril at a time
Get screened If you have diabetes youre more likely to suffer earlier and faster hearing loss probably because of impeded blood flow to nerves that control hearing If you have diabetes in particshyular you really should consider getting a yearly hearing test just as you get annual tests for vision kidney function and other possible dishyabetes complications says Nancy Vaughan PhD a researcher at the National Center for Rehabilitative Auditory Research in Portshyland Oregon who has investigated the diabetes-early-hearing-Ioss link Those with high blood pressure or high cholesterol could also benefit from regular hearing screenings she adds
Watch your aspirin Aspirin is among the 200 or so medicashytions that can cause hearing loss by damaging hearing hair cells
and nerves that carry sounds to the brain This is not to say you should ditch your daily aspirin therapy But it does mean you should be diligent about following the typical recommended dosages for heart health and pain--and not take much higher doses YoulI know youre taking too much aspirin if your ears ring but the ringing stops when you stop taking aspirin
Smell and Taste When smell is impaired an inability to taste usually follows This not only makes eating less pleasurable it can also lead to other problems Smell and taste get the digestive process rolling by triggering saliva and gastric juices to help digest food says Marcia Levin Pelchat PhD a scientist at Monell Chemical Senses Center in Philadelphia the nations leading institute for smell and taste research Before food is even eaten these senses allow the body to anticipate food and make absorpshytion more efficient And when you cant smell or taste food youre less likely to eat it risking malnutrition Chew over the following strategies for preserving the flavor in your life
Breathe in If youre sitting down for a hot meal says Alan Hirsch MD director of the Smell and Taste Treatment and Research Foundation in Chicago take advantage of the cool fact that its good to snifffood before you eat because heat aermiddot ates odor molecules that youll perceive as taste
Hit the showers A less practical but equally effective varishyation on the above principle The heat and humidity of a warm shower clears sinuses and helps dissolve molecules that facilishytate the ability to smell says Hirsch Plus youll be nice and clean for dinner
Manage your sniffles People with recurrent colds or allergy problems are more vulnerable to smell and taste impainnent feshycause they often develop nasal polyps that block the sense recepshytors inside the top of the nose Hirsch adds Its most noticeable while they have a cold or allergies but frequent nasal or sinus problems can lead to chronic problems in the ability to smell
But rethink that cold remedy A zinc deficiency is one suspected cause of smell problems but that doesnt mean cold remedies containing this nutrient are a cure-all Zinc lozenges such as Cold-Eeze and zinc nose sprays that you can buy over the counter actually cause a temporary distortion in smelJ and taste especially in sweet sensations says Pelchat When you stop using them your nonnal senses of smell and taste usually return
Buckle up The single most common cause of a complete smell impairment Head injury like that sustained in a car accident says Hirsch Perhaps the easiest thing you can do to protect your senses of smell and taste is to always wear a seat belt while driving
Sid KJrchheimer last wrote for AARP The Magazine about scams (HRip-off Alert July-August 2004) He is also the author of a forthshycoming action guide that collects hundreds of tips on how to avoid conshysumer rip-offs (AARP BooksSterling spring 2006)
bull __tHdWtr~~
From AARP The Magazine SeptemberOctober 200S pp 24-27 Copyright 0 2005 by Sid Kirchheimer Reprinted by permission of the author
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COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
I
Lecture Diagam of Sensory Processes
SENSORY PROCESSES
Optic mechanism
Auditory mechanism
Olfactory mechanism f
I I
IGustatory mechanism I
ICutaneous mechanisms I
I J
Recepcors Transduction
Retina bull rods bull cones
Organ or Coni
I Olfactcry- epithelium
Tasre cells Taste buds
Skin recepcors
1---11(Kinesthetic mechanism
IIVestibular mechanism
J
)
Visual acuiry Color blincness I l Lateral inhibitionJ
Piech and loudness t---til LocacionI
H t I
Free neJe endings Paradoxical cold
Heating IOS5I
I Pheromones
lensrrual synch rony I
I Tase blindness Taste aversionl
ltAcupunctUreI and more Relative temperaturel
4 JOints renoons t---- Internal reeaback and muscles)
Semicircular
canals J
I Tabes dorsalis
i Marion sickness
l Verti20
Centrifugal force
Referred painr-----1( All receptor r----tl~ Chronic painPain mechanisms ~~ems Acute pain
Introduction to Pdlol~ O1 Dr R~aJya M KiD
SENSATION AND PERCEPTION CONCEPT MAP
Sensation
N N
Depth Perception
cues
Environmenta Stimulation Transduction Sensation Perception
~ -- ~ - ~ light Waves I Nerve Impulses
IntrodMction to Psychology 201 Dr Roslllyn M King
II
Introduction to Psychology 201 Dr Rosalyn M King
Sensation
What is a sense What is sensation What is the difference between sensation and perception Develop a demonstration of how our sensory processes work and how perception kicks in
Ov What are the five primary senses with definition How does information from your senses get to your brain
o 1 What ispsychophysics Absolute thresholds can be amazingly low what are examples ofshystimuli at the absolute threshold for the five primary senses
o Define and describe sensitivity to stimuli and the signal detection theory Provide examples of the theory in every day life
o Define and describe Webers law and just-noticeable difference (JND) How can you judge the differences between s~imuli
o How would you describe vision What is required for vision Define and describe the accessory structures of the eye including the cornea pupil iris and lens Define the work of the retina and explain how accommodation affects the image on the retina
O Define photoreceptors rods and cones Describe how these structures are involved in transduction and dark adaptation Also describe how cones are involved in hue saturation and brightness
o Describe the path that visul information follows on its way to the brain including the roles of the optic nerve optic chiasm primary visual cortex and feature detectors What creates the blind spot
o Describe the tWo major theories of color vision
o Describe color blindness and its types What do color blind people see l o What are some visual disorders and diseases
o Describe the process ofcoding auditory information What structures of the ear are I involved Define each critical part 0 bull bull
o How do sound waves reach the brain I
--__----_ _---------_ ~-----~----
o Describe the theories of hearing pitch and how we locate sounds
o Describe the nature and causes of hearing loss and describe the effects of noise on hearing and behavior What types of hearing and deafness problems currently exist What is the cochlear implant and what does it do c
o Describe our sense of smell (olfaction) and our sense of taste (gustation) Describe the relationship among taste smell and flavor~ Why does food taste so bland when I have a cold Is there a relationship between smell and memory Between smell and depression Between smell and illness Which is greater- smell or taste
o Describe the transduction process in the olfactory system Discuss the path that olfactory information follows to the brain
o What are pheromones Describe taste buds
o Describe the somatosensory systems which are spread throughout the body Describe the transduction process in the skin senses including touch pain and temperature What does the sense of touch provide
o What is kinesthesia and the vestibular sense What do they provide
o Describe the gate control theory of pain What are the bodys natural analgesics
o Discuss the effects ofsensory restriction
mtToductioa 10 Psycbl)log~ 201 Dr R()lIal~n ~[ Kln~
StJ)tlRY NOTES ON SENSATION (HAI~1)OUT)
Overview of the Humaa Senses
KiDelthia The sense UuglvtZ us information about the location of our body parts and allow our nOVen1elt
Vetibular Setlc Our SclSe ofbalance Viud SenciE ves) Our visual C3ll1cra or window of the world Sight for most pcoplc is be nos imPOrtlllt way of gathering imormation about the world Hurm (Audition) Is feing1t a distance Iniorms us of pressure cbanges in the world illat 7l1y talce place many meters away Physical movement is the stimulus for heariDg Tutc(Gustat1og) ActS as1 gatciceper ro the digestive system by providiDg imormaticn about the substance that may or may not be ingested SweD (Olfaction) Functioos as a distancc sense Provides information about chemic31s suspencied in the air Warns of impending danger as when we sniff escaping gas Plays a role in identifying other pcsoos Touch (Skin Scn~es) Pressure warmth C()ld and pain Enables us to detect what is acijacent to our bodies
Buic Concepts in Sensation
Senorv ReceptOr responsible tor coding iDIormatioo by converting or tansducng raw physicd energy into neurti impulses wbich are then interpreted by our ccnn nervous system T randuction the tramlation of physical energy into electrical signal Sonsorv Deprivation Ii condition mwhich m organism is deprived ot sensory stimulation P3vchophvsio the study of the reiatiooship between the physical narure of stimuli and a persalls sensory rczpooses to lhen
Absolute Threshold det=mining the smallest magnitllde of a stimulus that em be reliably discriminaIed from no stimulus at all 50 pcrccnt ofthc time Sifai-Detection Theorv amp thcory that addresses the role of psyehologica(and other factorS such as costS and benefits) in our ability to identify stimuli D~iding whether we have detected a given stimulus Having [0 rely on p~ decisioo criteria Sennrv Adapt2tioD the reductioo or disappearance ofsensory responsiveness that occurs when stimulation is unchanging or repetitious Difference Threshold or Just NoticubJe Difference (JNl) the minimum difference in intensity that a stimulus em be discriminated Weber Law amp law swing that the smallest detectable diffirence (JND) for myintlnsity of a stimulus is a coostant function of the intcosity of the stimulus This coostanl VariCl tOr C3Ch of the sensory sysums
Vision P311S o(tbe EYe Cornea rUlspannt shield that COVe3 the front of the tye
Lens focuses Iiyenht rays iaIling on the retina Bemis incoming light waves into oarrow rays Pupil opening in the center ofthe iris that helps regulacc the amount of light passing into the reU chamber of the eye Iris Controls the amoUllt ofliglll that cntCS the Ite Retina Is the neural tissue lining the inside back surlacc of the ey~ it absorbs light procsscs images and sends visual intomlauoo to the brain The brains envoy in the eye Contains the Rods aad Canes JaiIling black and white and color vision Optic Nerve a bundle oineunl fibes that eat out the back oithe Ie Cmy oeural imOnnaUon to the brain
Viual Disorder of the Retina Blind Spou occur due [0 a hole in the retinas optic disk You cmnot see the part of he image that falls cn tt Nursightedness fMyoDiah the inability to see objectS far away The eeball is too long so that light from distallt objects focus in front of the retina Farsightedness rHVlJernpia) inability to see objects close up The efebailis too short LigiJt focusC$ on l
lOint bchmd the retina
Page Two) S ummary-SelltioD
C1taracu 311 opague film mat grows over the lens Glaucoma degeneration of the opuc nerve caused by a pressUre buildup withio the yebail due to biockages thaI meet the drainage of the 3CqUeoUS humor Other Visual Disorders Diabetic retinopathy macular degeneration deached reMa
Viual Receptors Rods and Cone Rods 3l1d cones are the pilotorecepton in the reuna rllCY contam chemicals thaI absorb ligbt waves Rods middotAre specialized visual receptors that playa leey role in night vision and periphera vision middotOperate at low light intClSiti= and lead to achromatic (colorless) SClSations -Transmit sensations oilight and darlc only
-You depend on rods for visioll in dim light middotRods cm see only shades of black white and gray -Rods oumumbercones by about 120 million to 7 million -Rods contam lightscnsitive chemical Cllled Rhodopin a necessary clecicd to make Vitamin A A deficiency in both rcsults in night blindneSl Cone middotPlay in key role in daylight vision color vision and fine detail -Conccalrltcti most heavily in the ccntcr of the retina in an area called the fovea -Conuins J chemicals called Iodopins whicplusmn1 are necessary for color vision
Dark Adapration is the process of adapting from bright light to dim light Lizht Adaptation is the process of adapting from darlc to light
Theories ot Color Vision Trichromatic Theo Discovcnd thaI there are J primary colors blue green and red which can be misxcd to form aU other colors Proposes that the human eye has 3 types of receptors with diffmning sensitivities to diifcnnt wavelengths Our ability to peneive a secmingly unlimited array ofcolon results from thejoint action of the tree rcceptor types Our perception of ail colors are plOduced tbrcUyenh comobinations of activity by these 3 types of receptors
People who see a fWl range ofcolorr are ctlled rrich romatJ becmsc they register all J color clwmels Dichromau have only 2 color channels Monochromats are completely blind to diffcrexs in color
The Opponent-Process Theon The theory that color vision is made possible by 3 types of cones some of which respond to red or gnen Jight some to blue or yellow and some only to the intensity of light This theory suggestS thaI above the aeunJ level of the ntina we possess six kinds of cells that playa role in sensatioQS ofcolor Twe of these handle red and green 0= is stimulated by red light and inhibited by green light wberess the other is stimulated by green light and moiled by red IigilL This is why it is C3Iled an opponent-proc=s Two additional cells handle yellow and blue oae is stimulated by yellow light and inhibited by blue while the other shows the opposite pamm The remaining two rypes handle black and white qaU1 in m opponcm process llWlIler
HEARING -The process funcrion or power ofperceiving sound The stimuli for heuing or audition are sound waves - High and low sounds cm be distinguised by their pitch -The e3lis the structure through which we percive sound P3rtS oiilie eu include outer (visible part-funnes soundwaves into e3r cma1 that strikes the eItdrum) middle (includes the hammer anvil stirrup and OVU window) and inner (contains the auditory receptorsmiddot the cochlea and basilar mcnbrane)
Theories otHearinlo Pitch Ptace TheG f)t Pitch The piech of a sound is determined by the plac slong the basilarlIlCnbrane that vibraus in nsponse to it The bigher the pitch of soum the closer the nsponsive IlelfOQS lie to the oval window
Page Three) Summary-SensaciOD
Frequency Theon of Pitch Pilch perception depends on the stimulation of neural impulses that match the frequency of the sound waves DupUdty Theon Pitch perception depends both on tbeplacc and frequency oineural response
TYpa ot Hearinl Problemll
Conduetfon De_fnen Hearing loss caU$Cd by wax or injwy Sellllo[-Neural Deafne Loss caused by injwy to the hair cells or audjtory nerves Damage IS irreversible Stimulation DeafDen Deafness due to exposure to sounds that are exccsslvely loud Centra Dearness Caused by disease and tumors in the audilOry pathways and cortex of the brain Untreatablc
Cochlear Implant An artificial hearing device implanted in the skull Motion Slslmell Involves strlCtuns in the inner ear - the vestibular organs
Ioucb A number of diffennt skin sensatioas After the free nerve endings convert pressure warmth cold and paiD into nerve impulses these impulses ultimately reach the somatosensory area of the cortex At this point you experience the sensation of touch
lm A sigual that somcthiDg is wrong in the body Eadorphins act to reduce pain Gat Control Theory otPaln Involves the brain providing insttuctions to neurons to reie3Se endorphins and block pain in the body
Tate Tute is I chemical sense that responds to the chemical stl1ICtUre of substances Four basic tastes sweet salty sour bitta
SmeU The seme ofsmell is ten thousand times more sensitive than taste The firing ofneurons transmits information about odors to the brain via the olfactory bulb
Popular Studies re olfaction
Menstrual Svnchrony Psychologisc Martha McClintock monitored the menstrual cycles of 13Swomen and found that the cycles offtiends and roommates converged due to their spending time in close quarters
Pbernmones Produced by other members of the species and detected through the sense of smell Example animaLs marking territory Scents induce mating behavior
Dr ROSMYII M XlIIK ntrotblcdoll to Psycllology Article 8
F 7 cmr g RB
Sensational Thne-ups Fifteen ways to improve your vision hearing taste and sense of smell
SID KIRCHHEIMER
Are people around you mumbling more often these days Does food seem to need an extra splash of Tabasco to please the palate Would the newspaper be easier to read
if your arms were just a few feet longer and the print a bit bigger Welcome to the club By the time we hit middle age most of
us suffer from some decline of the senses But dont despair There are ways to protect-and even improve-your ability to see hear smell and taste all of lifes offerings Experts we conshysulted recommend the following senses-sharpening middotstrategies
Sight Only reading glasses or other special eyewear can foil the common cause of weakened vision presbyopia the so-called aging eyes that result when the lens of the eye loses its flexishybility making it harder to focus clearly on close objects But you can take measures to stave off some of the leading causes of age-related blindness See if these work for you
Pop five a day A National Eye Institute study shows that one of the best ways to arrest macular degeneration is by following a simple five-pill supplement regimen daily doses of500 mg of vishytamin C 400 intemational units of vitamin E 15 mg of beta carshyotene 80 mg of zinc oxide and 2 mg of cupric oxide You really need to take these in supplement form because there is no way you could get these amounts from food alone says National Eye mstitute researcher Emily Chew MD
Loosenup A study in the British Journal of Ophthalmology finds that a tight necktie may increase risk of glaucoma by conshystricting neck veins boosting fluid pressure inside the eyes to dangerous levels No one says you have to strangle yourself says study author Robert Ritch MD of the New York Eye and Ear Infirmary If you cant get your finger in between your neck and your collar easily its too tight
Keep your specs on The mainstay material in prescription eyewear-polycarbonate lenses-helps block harmful ultravishyolet light a key cause of cataracts says ophthalmologist Wilshyliam Uoyd MD of UC Davis Medical Center So keep your glasses on whenever youre outdoors (or don prescription sunshyglasses) And if youre 2020 look for nonprescription sunshy
glasses at the drugstore or mall that are labeled to protect against both UV A and UVB rays
Plow Into power plants Some of the disease-protecting chemicals naturaIly found in fruits and vegetables also shield these plants from UV rays and other environmental pollutants that can damage your vision While most types of produce are beneficial peas peppers and green leafy vegetables such as kale romaine lettuce and spinach stand out because theyre rich in lutein and other key vision-protecting nutrients
Get an early start Eye-harming environmental pollutantsshysmog in plain Englisb-are at their lowest levels early in the day To limit your exposure to toxins in the air Lloyd suggests doing yani work exercise and other outdoor activities early in the moming
Hearing While illness injury overuse of certain drugs and genetics can all lead to hearing loss the primary reason most aging Amerishycans go deaf is their past exposure to noise With every noise that is loud or long enough some of the 6000 or so tiny hairs inside each ear that allow sound waves to be heard are permashynently damaged causing a gradual hearing loss that becomes noticeable in middle age and beyond Some sound advice
Plug em Wearing ear protection is the obvious way to protect these sensitive hair ceUs but you dont have to look like an aipOl1 bagshygage handlerwhile doing it Small foam plugs that discreetly fit in your ear may actually be better than the bulky padded earmuff types says David Nielsen MD of the American Academy of OtolaryngologyshyHead and Neck Surgery These plugs reduce noise by about 20 decishybels compared with the 15-decibel protection you get from more exshypensive padded earmuffs Plus the plugs are cooler he points out
Work out In silence Regular exercise keeps hearing sharp by improving or maintaining good blood flow to the inner ear But during exercise when more blood is feeding muscles less may get to nerves that control hearing making them more vulnerable to noise-caused damage Some studies indicate that loud music or noise heard during exercise may be more damaging than noise heard at the same volumes when youre sedentary Researchers are not unanishymous about this but unless you need to listen to loud music while you exe~~ you probably shouldnt says Nielsen
43
ANNUAL EDIT10NS
Spark Your Sixth Sense
Just for fun we asked leading experts what can be done to maintain or enhance the sixth sense -abilities such as ESP telepathy and clairvoyance It turns out psychic abilities may actually benefit from aging Conditions that are more conducive for psychic experiences seem to ocshycur more readily in older people than in younger ones says researcher Emily Williams Kelly PhD of the Unishyversity of Virginias division of personality studies which studies psychic phenomena How better to get in touch with the other side Consider the following
bull Use the quiet When the house is absent of yelling kids blaring music and other immediate distractions youre more likely to be able to focus on the beyond These events seem to occur more readily in those who have them with quiet solitude and meditation says Kelly
bull Watch for signs People who are extroverted and open to the idea of having these experiences are more likely to show ESP abilities says Kelly And their glass is half fullft attitude includes taking clues from everyday events middotSigns are everywhere adds Lisa Nash a clairvoyant and online psychic reader at Global Psychic Inc Pay attention to what you see while you are driving It may be an indication of whats in your lifes path A dead deer on the side of the road might indicate that you are neglecting your inner power that comes from gentleness
bull Eat for illumination Nash says many psychics eat healthfully avoiding alcohol and drugs as well as
caffeine sugar and processed foods in order to maintain mental focus and clarity Meanwhile recent research shows that one of the omega-3 fatty acids found in heart-healthy fish such as salmon and mackerel can prevent age-related damage to a part of the brain where cells responsible for learning and memory communicate with one another -SK
Dont be a blowhard Strenuous nose blowing can cause temporary or pennanent hearing loss by rupturing the delicate structures inside the eardrum To relieve nasal congestion adshyvises Nielsen gently blow one nostril at a time
Get screened If you have diabetes youre more likely to suffer earlier and faster hearing loss probably because of impeded blood flow to nerves that control hearing If you have diabetes in particshyular you really should consider getting a yearly hearing test just as you get annual tests for vision kidney function and other possible dishyabetes complications says Nancy Vaughan PhD a researcher at the National Center for Rehabilitative Auditory Research in Portshyland Oregon who has investigated the diabetes-early-hearing-Ioss link Those with high blood pressure or high cholesterol could also benefit from regular hearing screenings she adds
Watch your aspirin Aspirin is among the 200 or so medicashytions that can cause hearing loss by damaging hearing hair cells
and nerves that carry sounds to the brain This is not to say you should ditch your daily aspirin therapy But it does mean you should be diligent about following the typical recommended dosages for heart health and pain--and not take much higher doses YoulI know youre taking too much aspirin if your ears ring but the ringing stops when you stop taking aspirin
Smell and Taste When smell is impaired an inability to taste usually follows This not only makes eating less pleasurable it can also lead to other problems Smell and taste get the digestive process rolling by triggering saliva and gastric juices to help digest food says Marcia Levin Pelchat PhD a scientist at Monell Chemical Senses Center in Philadelphia the nations leading institute for smell and taste research Before food is even eaten these senses allow the body to anticipate food and make absorpshytion more efficient And when you cant smell or taste food youre less likely to eat it risking malnutrition Chew over the following strategies for preserving the flavor in your life
Breathe in If youre sitting down for a hot meal says Alan Hirsch MD director of the Smell and Taste Treatment and Research Foundation in Chicago take advantage of the cool fact that its good to snifffood before you eat because heat aermiddot ates odor molecules that youll perceive as taste
Hit the showers A less practical but equally effective varishyation on the above principle The heat and humidity of a warm shower clears sinuses and helps dissolve molecules that facilishytate the ability to smell says Hirsch Plus youll be nice and clean for dinner
Manage your sniffles People with recurrent colds or allergy problems are more vulnerable to smell and taste impainnent feshycause they often develop nasal polyps that block the sense recepshytors inside the top of the nose Hirsch adds Its most noticeable while they have a cold or allergies but frequent nasal or sinus problems can lead to chronic problems in the ability to smell
But rethink that cold remedy A zinc deficiency is one suspected cause of smell problems but that doesnt mean cold remedies containing this nutrient are a cure-all Zinc lozenges such as Cold-Eeze and zinc nose sprays that you can buy over the counter actually cause a temporary distortion in smelJ and taste especially in sweet sensations says Pelchat When you stop using them your nonnal senses of smell and taste usually return
Buckle up The single most common cause of a complete smell impairment Head injury like that sustained in a car accident says Hirsch Perhaps the easiest thing you can do to protect your senses of smell and taste is to always wear a seat belt while driving
Sid KJrchheimer last wrote for AARP The Magazine about scams (HRip-off Alert July-August 2004) He is also the author of a forthshycoming action guide that collects hundreds of tips on how to avoid conshysumer rip-offs (AARP BooksSterling spring 2006)
bull __tHdWtr~~
From AARP The Magazine SeptemberOctober 200S pp 24-27 Copyright 0 2005 by Sid Kirchheimer Reprinted by permission of the author
44
COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
SENSATION AND PERCEPTION CONCEPT MAP
Sensation
N N
Depth Perception
cues
Environmenta Stimulation Transduction Sensation Perception
~ -- ~ - ~ light Waves I Nerve Impulses
IntrodMction to Psychology 201 Dr Roslllyn M King
II
Introduction to Psychology 201 Dr Rosalyn M King
Sensation
What is a sense What is sensation What is the difference between sensation and perception Develop a demonstration of how our sensory processes work and how perception kicks in
Ov What are the five primary senses with definition How does information from your senses get to your brain
o 1 What ispsychophysics Absolute thresholds can be amazingly low what are examples ofshystimuli at the absolute threshold for the five primary senses
o Define and describe sensitivity to stimuli and the signal detection theory Provide examples of the theory in every day life
o Define and describe Webers law and just-noticeable difference (JND) How can you judge the differences between s~imuli
o How would you describe vision What is required for vision Define and describe the accessory structures of the eye including the cornea pupil iris and lens Define the work of the retina and explain how accommodation affects the image on the retina
O Define photoreceptors rods and cones Describe how these structures are involved in transduction and dark adaptation Also describe how cones are involved in hue saturation and brightness
o Describe the path that visul information follows on its way to the brain including the roles of the optic nerve optic chiasm primary visual cortex and feature detectors What creates the blind spot
o Describe the tWo major theories of color vision
o Describe color blindness and its types What do color blind people see l o What are some visual disorders and diseases
o Describe the process ofcoding auditory information What structures of the ear are I involved Define each critical part 0 bull bull
o How do sound waves reach the brain I
--__----_ _---------_ ~-----~----
o Describe the theories of hearing pitch and how we locate sounds
o Describe the nature and causes of hearing loss and describe the effects of noise on hearing and behavior What types of hearing and deafness problems currently exist What is the cochlear implant and what does it do c
o Describe our sense of smell (olfaction) and our sense of taste (gustation) Describe the relationship among taste smell and flavor~ Why does food taste so bland when I have a cold Is there a relationship between smell and memory Between smell and depression Between smell and illness Which is greater- smell or taste
o Describe the transduction process in the olfactory system Discuss the path that olfactory information follows to the brain
o What are pheromones Describe taste buds
o Describe the somatosensory systems which are spread throughout the body Describe the transduction process in the skin senses including touch pain and temperature What does the sense of touch provide
o What is kinesthesia and the vestibular sense What do they provide
o Describe the gate control theory of pain What are the bodys natural analgesics
o Discuss the effects ofsensory restriction
mtToductioa 10 Psycbl)log~ 201 Dr R()lIal~n ~[ Kln~
StJ)tlRY NOTES ON SENSATION (HAI~1)OUT)
Overview of the Humaa Senses
KiDelthia The sense UuglvtZ us information about the location of our body parts and allow our nOVen1elt
Vetibular Setlc Our SclSe ofbalance Viud SenciE ves) Our visual C3ll1cra or window of the world Sight for most pcoplc is be nos imPOrtlllt way of gathering imormation about the world Hurm (Audition) Is feing1t a distance Iniorms us of pressure cbanges in the world illat 7l1y talce place many meters away Physical movement is the stimulus for heariDg Tutc(Gustat1og) ActS as1 gatciceper ro the digestive system by providiDg imormaticn about the substance that may or may not be ingested SweD (Olfaction) Functioos as a distancc sense Provides information about chemic31s suspencied in the air Warns of impending danger as when we sniff escaping gas Plays a role in identifying other pcsoos Touch (Skin Scn~es) Pressure warmth C()ld and pain Enables us to detect what is acijacent to our bodies
Buic Concepts in Sensation
Senorv ReceptOr responsible tor coding iDIormatioo by converting or tansducng raw physicd energy into neurti impulses wbich are then interpreted by our ccnn nervous system T randuction the tramlation of physical energy into electrical signal Sonsorv Deprivation Ii condition mwhich m organism is deprived ot sensory stimulation P3vchophvsio the study of the reiatiooship between the physical narure of stimuli and a persalls sensory rczpooses to lhen
Absolute Threshold det=mining the smallest magnitllde of a stimulus that em be reliably discriminaIed from no stimulus at all 50 pcrccnt ofthc time Sifai-Detection Theorv amp thcory that addresses the role of psyehologica(and other factorS such as costS and benefits) in our ability to identify stimuli D~iding whether we have detected a given stimulus Having [0 rely on p~ decisioo criteria Sennrv Adapt2tioD the reductioo or disappearance ofsensory responsiveness that occurs when stimulation is unchanging or repetitious Difference Threshold or Just NoticubJe Difference (JNl) the minimum difference in intensity that a stimulus em be discriminated Weber Law amp law swing that the smallest detectable diffirence (JND) for myintlnsity of a stimulus is a coostant function of the intcosity of the stimulus This coostanl VariCl tOr C3Ch of the sensory sysums
Vision P311S o(tbe EYe Cornea rUlspannt shield that COVe3 the front of the tye
Lens focuses Iiyenht rays iaIling on the retina Bemis incoming light waves into oarrow rays Pupil opening in the center ofthe iris that helps regulacc the amount of light passing into the reU chamber of the eye Iris Controls the amoUllt ofliglll that cntCS the Ite Retina Is the neural tissue lining the inside back surlacc of the ey~ it absorbs light procsscs images and sends visual intomlauoo to the brain The brains envoy in the eye Contains the Rods aad Canes JaiIling black and white and color vision Optic Nerve a bundle oineunl fibes that eat out the back oithe Ie Cmy oeural imOnnaUon to the brain
Viual Disorder of the Retina Blind Spou occur due [0 a hole in the retinas optic disk You cmnot see the part of he image that falls cn tt Nursightedness fMyoDiah the inability to see objectS far away The eeball is too long so that light from distallt objects focus in front of the retina Farsightedness rHVlJernpia) inability to see objects close up The efebailis too short LigiJt focusC$ on l
lOint bchmd the retina
Page Two) S ummary-SelltioD
C1taracu 311 opague film mat grows over the lens Glaucoma degeneration of the opuc nerve caused by a pressUre buildup withio the yebail due to biockages thaI meet the drainage of the 3CqUeoUS humor Other Visual Disorders Diabetic retinopathy macular degeneration deached reMa
Viual Receptors Rods and Cone Rods 3l1d cones are the pilotorecepton in the reuna rllCY contam chemicals thaI absorb ligbt waves Rods middotAre specialized visual receptors that playa leey role in night vision and periphera vision middotOperate at low light intClSiti= and lead to achromatic (colorless) SClSations -Transmit sensations oilight and darlc only
-You depend on rods for visioll in dim light middotRods cm see only shades of black white and gray -Rods oumumbercones by about 120 million to 7 million -Rods contam lightscnsitive chemical Cllled Rhodopin a necessary clecicd to make Vitamin A A deficiency in both rcsults in night blindneSl Cone middotPlay in key role in daylight vision color vision and fine detail -Conccalrltcti most heavily in the ccntcr of the retina in an area called the fovea -Conuins J chemicals called Iodopins whicplusmn1 are necessary for color vision
Dark Adapration is the process of adapting from bright light to dim light Lizht Adaptation is the process of adapting from darlc to light
Theories ot Color Vision Trichromatic Theo Discovcnd thaI there are J primary colors blue green and red which can be misxcd to form aU other colors Proposes that the human eye has 3 types of receptors with diffmning sensitivities to diifcnnt wavelengths Our ability to peneive a secmingly unlimited array ofcolon results from thejoint action of the tree rcceptor types Our perception of ail colors are plOduced tbrcUyenh comobinations of activity by these 3 types of receptors
People who see a fWl range ofcolorr are ctlled rrich romatJ becmsc they register all J color clwmels Dichromau have only 2 color channels Monochromats are completely blind to diffcrexs in color
The Opponent-Process Theon The theory that color vision is made possible by 3 types of cones some of which respond to red or gnen Jight some to blue or yellow and some only to the intensity of light This theory suggestS thaI above the aeunJ level of the ntina we possess six kinds of cells that playa role in sensatioQS ofcolor Twe of these handle red and green 0= is stimulated by red light and inhibited by green light wberess the other is stimulated by green light and moiled by red IigilL This is why it is C3Iled an opponent-proc=s Two additional cells handle yellow and blue oae is stimulated by yellow light and inhibited by blue while the other shows the opposite pamm The remaining two rypes handle black and white qaU1 in m opponcm process llWlIler
HEARING -The process funcrion or power ofperceiving sound The stimuli for heuing or audition are sound waves - High and low sounds cm be distinguised by their pitch -The e3lis the structure through which we percive sound P3rtS oiilie eu include outer (visible part-funnes soundwaves into e3r cma1 that strikes the eItdrum) middle (includes the hammer anvil stirrup and OVU window) and inner (contains the auditory receptorsmiddot the cochlea and basilar mcnbrane)
Theories otHearinlo Pitch Ptace TheG f)t Pitch The piech of a sound is determined by the plac slong the basilarlIlCnbrane that vibraus in nsponse to it The bigher the pitch of soum the closer the nsponsive IlelfOQS lie to the oval window
Page Three) Summary-SensaciOD
Frequency Theon of Pitch Pilch perception depends on the stimulation of neural impulses that match the frequency of the sound waves DupUdty Theon Pitch perception depends both on tbeplacc and frequency oineural response
TYpa ot Hearinl Problemll
Conduetfon De_fnen Hearing loss caU$Cd by wax or injwy Sellllo[-Neural Deafne Loss caused by injwy to the hair cells or audjtory nerves Damage IS irreversible Stimulation DeafDen Deafness due to exposure to sounds that are exccsslvely loud Centra Dearness Caused by disease and tumors in the audilOry pathways and cortex of the brain Untreatablc
Cochlear Implant An artificial hearing device implanted in the skull Motion Slslmell Involves strlCtuns in the inner ear - the vestibular organs
Ioucb A number of diffennt skin sensatioas After the free nerve endings convert pressure warmth cold and paiD into nerve impulses these impulses ultimately reach the somatosensory area of the cortex At this point you experience the sensation of touch
lm A sigual that somcthiDg is wrong in the body Eadorphins act to reduce pain Gat Control Theory otPaln Involves the brain providing insttuctions to neurons to reie3Se endorphins and block pain in the body
Tate Tute is I chemical sense that responds to the chemical stl1ICtUre of substances Four basic tastes sweet salty sour bitta
SmeU The seme ofsmell is ten thousand times more sensitive than taste The firing ofneurons transmits information about odors to the brain via the olfactory bulb
Popular Studies re olfaction
Menstrual Svnchrony Psychologisc Martha McClintock monitored the menstrual cycles of 13Swomen and found that the cycles offtiends and roommates converged due to their spending time in close quarters
Pbernmones Produced by other members of the species and detected through the sense of smell Example animaLs marking territory Scents induce mating behavior
Dr ROSMYII M XlIIK ntrotblcdoll to Psycllology Article 8
F 7 cmr g RB
Sensational Thne-ups Fifteen ways to improve your vision hearing taste and sense of smell
SID KIRCHHEIMER
Are people around you mumbling more often these days Does food seem to need an extra splash of Tabasco to please the palate Would the newspaper be easier to read
if your arms were just a few feet longer and the print a bit bigger Welcome to the club By the time we hit middle age most of
us suffer from some decline of the senses But dont despair There are ways to protect-and even improve-your ability to see hear smell and taste all of lifes offerings Experts we conshysulted recommend the following senses-sharpening middotstrategies
Sight Only reading glasses or other special eyewear can foil the common cause of weakened vision presbyopia the so-called aging eyes that result when the lens of the eye loses its flexishybility making it harder to focus clearly on close objects But you can take measures to stave off some of the leading causes of age-related blindness See if these work for you
Pop five a day A National Eye Institute study shows that one of the best ways to arrest macular degeneration is by following a simple five-pill supplement regimen daily doses of500 mg of vishytamin C 400 intemational units of vitamin E 15 mg of beta carshyotene 80 mg of zinc oxide and 2 mg of cupric oxide You really need to take these in supplement form because there is no way you could get these amounts from food alone says National Eye mstitute researcher Emily Chew MD
Loosenup A study in the British Journal of Ophthalmology finds that a tight necktie may increase risk of glaucoma by conshystricting neck veins boosting fluid pressure inside the eyes to dangerous levels No one says you have to strangle yourself says study author Robert Ritch MD of the New York Eye and Ear Infirmary If you cant get your finger in between your neck and your collar easily its too tight
Keep your specs on The mainstay material in prescription eyewear-polycarbonate lenses-helps block harmful ultravishyolet light a key cause of cataracts says ophthalmologist Wilshyliam Uoyd MD of UC Davis Medical Center So keep your glasses on whenever youre outdoors (or don prescription sunshyglasses) And if youre 2020 look for nonprescription sunshy
glasses at the drugstore or mall that are labeled to protect against both UV A and UVB rays
Plow Into power plants Some of the disease-protecting chemicals naturaIly found in fruits and vegetables also shield these plants from UV rays and other environmental pollutants that can damage your vision While most types of produce are beneficial peas peppers and green leafy vegetables such as kale romaine lettuce and spinach stand out because theyre rich in lutein and other key vision-protecting nutrients
Get an early start Eye-harming environmental pollutantsshysmog in plain Englisb-are at their lowest levels early in the day To limit your exposure to toxins in the air Lloyd suggests doing yani work exercise and other outdoor activities early in the moming
Hearing While illness injury overuse of certain drugs and genetics can all lead to hearing loss the primary reason most aging Amerishycans go deaf is their past exposure to noise With every noise that is loud or long enough some of the 6000 or so tiny hairs inside each ear that allow sound waves to be heard are permashynently damaged causing a gradual hearing loss that becomes noticeable in middle age and beyond Some sound advice
Plug em Wearing ear protection is the obvious way to protect these sensitive hair ceUs but you dont have to look like an aipOl1 bagshygage handlerwhile doing it Small foam plugs that discreetly fit in your ear may actually be better than the bulky padded earmuff types says David Nielsen MD of the American Academy of OtolaryngologyshyHead and Neck Surgery These plugs reduce noise by about 20 decishybels compared with the 15-decibel protection you get from more exshypensive padded earmuffs Plus the plugs are cooler he points out
Work out In silence Regular exercise keeps hearing sharp by improving or maintaining good blood flow to the inner ear But during exercise when more blood is feeding muscles less may get to nerves that control hearing making them more vulnerable to noise-caused damage Some studies indicate that loud music or noise heard during exercise may be more damaging than noise heard at the same volumes when youre sedentary Researchers are not unanishymous about this but unless you need to listen to loud music while you exe~~ you probably shouldnt says Nielsen
43
ANNUAL EDIT10NS
Spark Your Sixth Sense
Just for fun we asked leading experts what can be done to maintain or enhance the sixth sense -abilities such as ESP telepathy and clairvoyance It turns out psychic abilities may actually benefit from aging Conditions that are more conducive for psychic experiences seem to ocshycur more readily in older people than in younger ones says researcher Emily Williams Kelly PhD of the Unishyversity of Virginias division of personality studies which studies psychic phenomena How better to get in touch with the other side Consider the following
bull Use the quiet When the house is absent of yelling kids blaring music and other immediate distractions youre more likely to be able to focus on the beyond These events seem to occur more readily in those who have them with quiet solitude and meditation says Kelly
bull Watch for signs People who are extroverted and open to the idea of having these experiences are more likely to show ESP abilities says Kelly And their glass is half fullft attitude includes taking clues from everyday events middotSigns are everywhere adds Lisa Nash a clairvoyant and online psychic reader at Global Psychic Inc Pay attention to what you see while you are driving It may be an indication of whats in your lifes path A dead deer on the side of the road might indicate that you are neglecting your inner power that comes from gentleness
bull Eat for illumination Nash says many psychics eat healthfully avoiding alcohol and drugs as well as
caffeine sugar and processed foods in order to maintain mental focus and clarity Meanwhile recent research shows that one of the omega-3 fatty acids found in heart-healthy fish such as salmon and mackerel can prevent age-related damage to a part of the brain where cells responsible for learning and memory communicate with one another -SK
Dont be a blowhard Strenuous nose blowing can cause temporary or pennanent hearing loss by rupturing the delicate structures inside the eardrum To relieve nasal congestion adshyvises Nielsen gently blow one nostril at a time
Get screened If you have diabetes youre more likely to suffer earlier and faster hearing loss probably because of impeded blood flow to nerves that control hearing If you have diabetes in particshyular you really should consider getting a yearly hearing test just as you get annual tests for vision kidney function and other possible dishyabetes complications says Nancy Vaughan PhD a researcher at the National Center for Rehabilitative Auditory Research in Portshyland Oregon who has investigated the diabetes-early-hearing-Ioss link Those with high blood pressure or high cholesterol could also benefit from regular hearing screenings she adds
Watch your aspirin Aspirin is among the 200 or so medicashytions that can cause hearing loss by damaging hearing hair cells
and nerves that carry sounds to the brain This is not to say you should ditch your daily aspirin therapy But it does mean you should be diligent about following the typical recommended dosages for heart health and pain--and not take much higher doses YoulI know youre taking too much aspirin if your ears ring but the ringing stops when you stop taking aspirin
Smell and Taste When smell is impaired an inability to taste usually follows This not only makes eating less pleasurable it can also lead to other problems Smell and taste get the digestive process rolling by triggering saliva and gastric juices to help digest food says Marcia Levin Pelchat PhD a scientist at Monell Chemical Senses Center in Philadelphia the nations leading institute for smell and taste research Before food is even eaten these senses allow the body to anticipate food and make absorpshytion more efficient And when you cant smell or taste food youre less likely to eat it risking malnutrition Chew over the following strategies for preserving the flavor in your life
Breathe in If youre sitting down for a hot meal says Alan Hirsch MD director of the Smell and Taste Treatment and Research Foundation in Chicago take advantage of the cool fact that its good to snifffood before you eat because heat aermiddot ates odor molecules that youll perceive as taste
Hit the showers A less practical but equally effective varishyation on the above principle The heat and humidity of a warm shower clears sinuses and helps dissolve molecules that facilishytate the ability to smell says Hirsch Plus youll be nice and clean for dinner
Manage your sniffles People with recurrent colds or allergy problems are more vulnerable to smell and taste impainnent feshycause they often develop nasal polyps that block the sense recepshytors inside the top of the nose Hirsch adds Its most noticeable while they have a cold or allergies but frequent nasal or sinus problems can lead to chronic problems in the ability to smell
But rethink that cold remedy A zinc deficiency is one suspected cause of smell problems but that doesnt mean cold remedies containing this nutrient are a cure-all Zinc lozenges such as Cold-Eeze and zinc nose sprays that you can buy over the counter actually cause a temporary distortion in smelJ and taste especially in sweet sensations says Pelchat When you stop using them your nonnal senses of smell and taste usually return
Buckle up The single most common cause of a complete smell impairment Head injury like that sustained in a car accident says Hirsch Perhaps the easiest thing you can do to protect your senses of smell and taste is to always wear a seat belt while driving
Sid KJrchheimer last wrote for AARP The Magazine about scams (HRip-off Alert July-August 2004) He is also the author of a forthshycoming action guide that collects hundreds of tips on how to avoid conshysumer rip-offs (AARP BooksSterling spring 2006)
bull __tHdWtr~~
From AARP The Magazine SeptemberOctober 200S pp 24-27 Copyright 0 2005 by Sid Kirchheimer Reprinted by permission of the author
44
COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
II
Introduction to Psychology 201 Dr Rosalyn M King
Sensation
What is a sense What is sensation What is the difference between sensation and perception Develop a demonstration of how our sensory processes work and how perception kicks in
Ov What are the five primary senses with definition How does information from your senses get to your brain
o 1 What ispsychophysics Absolute thresholds can be amazingly low what are examples ofshystimuli at the absolute threshold for the five primary senses
o Define and describe sensitivity to stimuli and the signal detection theory Provide examples of the theory in every day life
o Define and describe Webers law and just-noticeable difference (JND) How can you judge the differences between s~imuli
o How would you describe vision What is required for vision Define and describe the accessory structures of the eye including the cornea pupil iris and lens Define the work of the retina and explain how accommodation affects the image on the retina
O Define photoreceptors rods and cones Describe how these structures are involved in transduction and dark adaptation Also describe how cones are involved in hue saturation and brightness
o Describe the path that visul information follows on its way to the brain including the roles of the optic nerve optic chiasm primary visual cortex and feature detectors What creates the blind spot
o Describe the tWo major theories of color vision
o Describe color blindness and its types What do color blind people see l o What are some visual disorders and diseases
o Describe the process ofcoding auditory information What structures of the ear are I involved Define each critical part 0 bull bull
o How do sound waves reach the brain I
--__----_ _---------_ ~-----~----
o Describe the theories of hearing pitch and how we locate sounds
o Describe the nature and causes of hearing loss and describe the effects of noise on hearing and behavior What types of hearing and deafness problems currently exist What is the cochlear implant and what does it do c
o Describe our sense of smell (olfaction) and our sense of taste (gustation) Describe the relationship among taste smell and flavor~ Why does food taste so bland when I have a cold Is there a relationship between smell and memory Between smell and depression Between smell and illness Which is greater- smell or taste
o Describe the transduction process in the olfactory system Discuss the path that olfactory information follows to the brain
o What are pheromones Describe taste buds
o Describe the somatosensory systems which are spread throughout the body Describe the transduction process in the skin senses including touch pain and temperature What does the sense of touch provide
o What is kinesthesia and the vestibular sense What do they provide
o Describe the gate control theory of pain What are the bodys natural analgesics
o Discuss the effects ofsensory restriction
mtToductioa 10 Psycbl)log~ 201 Dr R()lIal~n ~[ Kln~
StJ)tlRY NOTES ON SENSATION (HAI~1)OUT)
Overview of the Humaa Senses
KiDelthia The sense UuglvtZ us information about the location of our body parts and allow our nOVen1elt
Vetibular Setlc Our SclSe ofbalance Viud SenciE ves) Our visual C3ll1cra or window of the world Sight for most pcoplc is be nos imPOrtlllt way of gathering imormation about the world Hurm (Audition) Is feing1t a distance Iniorms us of pressure cbanges in the world illat 7l1y talce place many meters away Physical movement is the stimulus for heariDg Tutc(Gustat1og) ActS as1 gatciceper ro the digestive system by providiDg imormaticn about the substance that may or may not be ingested SweD (Olfaction) Functioos as a distancc sense Provides information about chemic31s suspencied in the air Warns of impending danger as when we sniff escaping gas Plays a role in identifying other pcsoos Touch (Skin Scn~es) Pressure warmth C()ld and pain Enables us to detect what is acijacent to our bodies
Buic Concepts in Sensation
Senorv ReceptOr responsible tor coding iDIormatioo by converting or tansducng raw physicd energy into neurti impulses wbich are then interpreted by our ccnn nervous system T randuction the tramlation of physical energy into electrical signal Sonsorv Deprivation Ii condition mwhich m organism is deprived ot sensory stimulation P3vchophvsio the study of the reiatiooship between the physical narure of stimuli and a persalls sensory rczpooses to lhen
Absolute Threshold det=mining the smallest magnitllde of a stimulus that em be reliably discriminaIed from no stimulus at all 50 pcrccnt ofthc time Sifai-Detection Theorv amp thcory that addresses the role of psyehologica(and other factorS such as costS and benefits) in our ability to identify stimuli D~iding whether we have detected a given stimulus Having [0 rely on p~ decisioo criteria Sennrv Adapt2tioD the reductioo or disappearance ofsensory responsiveness that occurs when stimulation is unchanging or repetitious Difference Threshold or Just NoticubJe Difference (JNl) the minimum difference in intensity that a stimulus em be discriminated Weber Law amp law swing that the smallest detectable diffirence (JND) for myintlnsity of a stimulus is a coostant function of the intcosity of the stimulus This coostanl VariCl tOr C3Ch of the sensory sysums
Vision P311S o(tbe EYe Cornea rUlspannt shield that COVe3 the front of the tye
Lens focuses Iiyenht rays iaIling on the retina Bemis incoming light waves into oarrow rays Pupil opening in the center ofthe iris that helps regulacc the amount of light passing into the reU chamber of the eye Iris Controls the amoUllt ofliglll that cntCS the Ite Retina Is the neural tissue lining the inside back surlacc of the ey~ it absorbs light procsscs images and sends visual intomlauoo to the brain The brains envoy in the eye Contains the Rods aad Canes JaiIling black and white and color vision Optic Nerve a bundle oineunl fibes that eat out the back oithe Ie Cmy oeural imOnnaUon to the brain
Viual Disorder of the Retina Blind Spou occur due [0 a hole in the retinas optic disk You cmnot see the part of he image that falls cn tt Nursightedness fMyoDiah the inability to see objectS far away The eeball is too long so that light from distallt objects focus in front of the retina Farsightedness rHVlJernpia) inability to see objects close up The efebailis too short LigiJt focusC$ on l
lOint bchmd the retina
Page Two) S ummary-SelltioD
C1taracu 311 opague film mat grows over the lens Glaucoma degeneration of the opuc nerve caused by a pressUre buildup withio the yebail due to biockages thaI meet the drainage of the 3CqUeoUS humor Other Visual Disorders Diabetic retinopathy macular degeneration deached reMa
Viual Receptors Rods and Cone Rods 3l1d cones are the pilotorecepton in the reuna rllCY contam chemicals thaI absorb ligbt waves Rods middotAre specialized visual receptors that playa leey role in night vision and periphera vision middotOperate at low light intClSiti= and lead to achromatic (colorless) SClSations -Transmit sensations oilight and darlc only
-You depend on rods for visioll in dim light middotRods cm see only shades of black white and gray -Rods oumumbercones by about 120 million to 7 million -Rods contam lightscnsitive chemical Cllled Rhodopin a necessary clecicd to make Vitamin A A deficiency in both rcsults in night blindneSl Cone middotPlay in key role in daylight vision color vision and fine detail -Conccalrltcti most heavily in the ccntcr of the retina in an area called the fovea -Conuins J chemicals called Iodopins whicplusmn1 are necessary for color vision
Dark Adapration is the process of adapting from bright light to dim light Lizht Adaptation is the process of adapting from darlc to light
Theories ot Color Vision Trichromatic Theo Discovcnd thaI there are J primary colors blue green and red which can be misxcd to form aU other colors Proposes that the human eye has 3 types of receptors with diffmning sensitivities to diifcnnt wavelengths Our ability to peneive a secmingly unlimited array ofcolon results from thejoint action of the tree rcceptor types Our perception of ail colors are plOduced tbrcUyenh comobinations of activity by these 3 types of receptors
People who see a fWl range ofcolorr are ctlled rrich romatJ becmsc they register all J color clwmels Dichromau have only 2 color channels Monochromats are completely blind to diffcrexs in color
The Opponent-Process Theon The theory that color vision is made possible by 3 types of cones some of which respond to red or gnen Jight some to blue or yellow and some only to the intensity of light This theory suggestS thaI above the aeunJ level of the ntina we possess six kinds of cells that playa role in sensatioQS ofcolor Twe of these handle red and green 0= is stimulated by red light and inhibited by green light wberess the other is stimulated by green light and moiled by red IigilL This is why it is C3Iled an opponent-proc=s Two additional cells handle yellow and blue oae is stimulated by yellow light and inhibited by blue while the other shows the opposite pamm The remaining two rypes handle black and white qaU1 in m opponcm process llWlIler
HEARING -The process funcrion or power ofperceiving sound The stimuli for heuing or audition are sound waves - High and low sounds cm be distinguised by their pitch -The e3lis the structure through which we percive sound P3rtS oiilie eu include outer (visible part-funnes soundwaves into e3r cma1 that strikes the eItdrum) middle (includes the hammer anvil stirrup and OVU window) and inner (contains the auditory receptorsmiddot the cochlea and basilar mcnbrane)
Theories otHearinlo Pitch Ptace TheG f)t Pitch The piech of a sound is determined by the plac slong the basilarlIlCnbrane that vibraus in nsponse to it The bigher the pitch of soum the closer the nsponsive IlelfOQS lie to the oval window
Page Three) Summary-SensaciOD
Frequency Theon of Pitch Pilch perception depends on the stimulation of neural impulses that match the frequency of the sound waves DupUdty Theon Pitch perception depends both on tbeplacc and frequency oineural response
TYpa ot Hearinl Problemll
Conduetfon De_fnen Hearing loss caU$Cd by wax or injwy Sellllo[-Neural Deafne Loss caused by injwy to the hair cells or audjtory nerves Damage IS irreversible Stimulation DeafDen Deafness due to exposure to sounds that are exccsslvely loud Centra Dearness Caused by disease and tumors in the audilOry pathways and cortex of the brain Untreatablc
Cochlear Implant An artificial hearing device implanted in the skull Motion Slslmell Involves strlCtuns in the inner ear - the vestibular organs
Ioucb A number of diffennt skin sensatioas After the free nerve endings convert pressure warmth cold and paiD into nerve impulses these impulses ultimately reach the somatosensory area of the cortex At this point you experience the sensation of touch
lm A sigual that somcthiDg is wrong in the body Eadorphins act to reduce pain Gat Control Theory otPaln Involves the brain providing insttuctions to neurons to reie3Se endorphins and block pain in the body
Tate Tute is I chemical sense that responds to the chemical stl1ICtUre of substances Four basic tastes sweet salty sour bitta
SmeU The seme ofsmell is ten thousand times more sensitive than taste The firing ofneurons transmits information about odors to the brain via the olfactory bulb
Popular Studies re olfaction
Menstrual Svnchrony Psychologisc Martha McClintock monitored the menstrual cycles of 13Swomen and found that the cycles offtiends and roommates converged due to their spending time in close quarters
Pbernmones Produced by other members of the species and detected through the sense of smell Example animaLs marking territory Scents induce mating behavior
Dr ROSMYII M XlIIK ntrotblcdoll to Psycllology Article 8
F 7 cmr g RB
Sensational Thne-ups Fifteen ways to improve your vision hearing taste and sense of smell
SID KIRCHHEIMER
Are people around you mumbling more often these days Does food seem to need an extra splash of Tabasco to please the palate Would the newspaper be easier to read
if your arms were just a few feet longer and the print a bit bigger Welcome to the club By the time we hit middle age most of
us suffer from some decline of the senses But dont despair There are ways to protect-and even improve-your ability to see hear smell and taste all of lifes offerings Experts we conshysulted recommend the following senses-sharpening middotstrategies
Sight Only reading glasses or other special eyewear can foil the common cause of weakened vision presbyopia the so-called aging eyes that result when the lens of the eye loses its flexishybility making it harder to focus clearly on close objects But you can take measures to stave off some of the leading causes of age-related blindness See if these work for you
Pop five a day A National Eye Institute study shows that one of the best ways to arrest macular degeneration is by following a simple five-pill supplement regimen daily doses of500 mg of vishytamin C 400 intemational units of vitamin E 15 mg of beta carshyotene 80 mg of zinc oxide and 2 mg of cupric oxide You really need to take these in supplement form because there is no way you could get these amounts from food alone says National Eye mstitute researcher Emily Chew MD
Loosenup A study in the British Journal of Ophthalmology finds that a tight necktie may increase risk of glaucoma by conshystricting neck veins boosting fluid pressure inside the eyes to dangerous levels No one says you have to strangle yourself says study author Robert Ritch MD of the New York Eye and Ear Infirmary If you cant get your finger in between your neck and your collar easily its too tight
Keep your specs on The mainstay material in prescription eyewear-polycarbonate lenses-helps block harmful ultravishyolet light a key cause of cataracts says ophthalmologist Wilshyliam Uoyd MD of UC Davis Medical Center So keep your glasses on whenever youre outdoors (or don prescription sunshyglasses) And if youre 2020 look for nonprescription sunshy
glasses at the drugstore or mall that are labeled to protect against both UV A and UVB rays
Plow Into power plants Some of the disease-protecting chemicals naturaIly found in fruits and vegetables also shield these plants from UV rays and other environmental pollutants that can damage your vision While most types of produce are beneficial peas peppers and green leafy vegetables such as kale romaine lettuce and spinach stand out because theyre rich in lutein and other key vision-protecting nutrients
Get an early start Eye-harming environmental pollutantsshysmog in plain Englisb-are at their lowest levels early in the day To limit your exposure to toxins in the air Lloyd suggests doing yani work exercise and other outdoor activities early in the moming
Hearing While illness injury overuse of certain drugs and genetics can all lead to hearing loss the primary reason most aging Amerishycans go deaf is their past exposure to noise With every noise that is loud or long enough some of the 6000 or so tiny hairs inside each ear that allow sound waves to be heard are permashynently damaged causing a gradual hearing loss that becomes noticeable in middle age and beyond Some sound advice
Plug em Wearing ear protection is the obvious way to protect these sensitive hair ceUs but you dont have to look like an aipOl1 bagshygage handlerwhile doing it Small foam plugs that discreetly fit in your ear may actually be better than the bulky padded earmuff types says David Nielsen MD of the American Academy of OtolaryngologyshyHead and Neck Surgery These plugs reduce noise by about 20 decishybels compared with the 15-decibel protection you get from more exshypensive padded earmuffs Plus the plugs are cooler he points out
Work out In silence Regular exercise keeps hearing sharp by improving or maintaining good blood flow to the inner ear But during exercise when more blood is feeding muscles less may get to nerves that control hearing making them more vulnerable to noise-caused damage Some studies indicate that loud music or noise heard during exercise may be more damaging than noise heard at the same volumes when youre sedentary Researchers are not unanishymous about this but unless you need to listen to loud music while you exe~~ you probably shouldnt says Nielsen
43
ANNUAL EDIT10NS
Spark Your Sixth Sense
Just for fun we asked leading experts what can be done to maintain or enhance the sixth sense -abilities such as ESP telepathy and clairvoyance It turns out psychic abilities may actually benefit from aging Conditions that are more conducive for psychic experiences seem to ocshycur more readily in older people than in younger ones says researcher Emily Williams Kelly PhD of the Unishyversity of Virginias division of personality studies which studies psychic phenomena How better to get in touch with the other side Consider the following
bull Use the quiet When the house is absent of yelling kids blaring music and other immediate distractions youre more likely to be able to focus on the beyond These events seem to occur more readily in those who have them with quiet solitude and meditation says Kelly
bull Watch for signs People who are extroverted and open to the idea of having these experiences are more likely to show ESP abilities says Kelly And their glass is half fullft attitude includes taking clues from everyday events middotSigns are everywhere adds Lisa Nash a clairvoyant and online psychic reader at Global Psychic Inc Pay attention to what you see while you are driving It may be an indication of whats in your lifes path A dead deer on the side of the road might indicate that you are neglecting your inner power that comes from gentleness
bull Eat for illumination Nash says many psychics eat healthfully avoiding alcohol and drugs as well as
caffeine sugar and processed foods in order to maintain mental focus and clarity Meanwhile recent research shows that one of the omega-3 fatty acids found in heart-healthy fish such as salmon and mackerel can prevent age-related damage to a part of the brain where cells responsible for learning and memory communicate with one another -SK
Dont be a blowhard Strenuous nose blowing can cause temporary or pennanent hearing loss by rupturing the delicate structures inside the eardrum To relieve nasal congestion adshyvises Nielsen gently blow one nostril at a time
Get screened If you have diabetes youre more likely to suffer earlier and faster hearing loss probably because of impeded blood flow to nerves that control hearing If you have diabetes in particshyular you really should consider getting a yearly hearing test just as you get annual tests for vision kidney function and other possible dishyabetes complications says Nancy Vaughan PhD a researcher at the National Center for Rehabilitative Auditory Research in Portshyland Oregon who has investigated the diabetes-early-hearing-Ioss link Those with high blood pressure or high cholesterol could also benefit from regular hearing screenings she adds
Watch your aspirin Aspirin is among the 200 or so medicashytions that can cause hearing loss by damaging hearing hair cells
and nerves that carry sounds to the brain This is not to say you should ditch your daily aspirin therapy But it does mean you should be diligent about following the typical recommended dosages for heart health and pain--and not take much higher doses YoulI know youre taking too much aspirin if your ears ring but the ringing stops when you stop taking aspirin
Smell and Taste When smell is impaired an inability to taste usually follows This not only makes eating less pleasurable it can also lead to other problems Smell and taste get the digestive process rolling by triggering saliva and gastric juices to help digest food says Marcia Levin Pelchat PhD a scientist at Monell Chemical Senses Center in Philadelphia the nations leading institute for smell and taste research Before food is even eaten these senses allow the body to anticipate food and make absorpshytion more efficient And when you cant smell or taste food youre less likely to eat it risking malnutrition Chew over the following strategies for preserving the flavor in your life
Breathe in If youre sitting down for a hot meal says Alan Hirsch MD director of the Smell and Taste Treatment and Research Foundation in Chicago take advantage of the cool fact that its good to snifffood before you eat because heat aermiddot ates odor molecules that youll perceive as taste
Hit the showers A less practical but equally effective varishyation on the above principle The heat and humidity of a warm shower clears sinuses and helps dissolve molecules that facilishytate the ability to smell says Hirsch Plus youll be nice and clean for dinner
Manage your sniffles People with recurrent colds or allergy problems are more vulnerable to smell and taste impainnent feshycause they often develop nasal polyps that block the sense recepshytors inside the top of the nose Hirsch adds Its most noticeable while they have a cold or allergies but frequent nasal or sinus problems can lead to chronic problems in the ability to smell
But rethink that cold remedy A zinc deficiency is one suspected cause of smell problems but that doesnt mean cold remedies containing this nutrient are a cure-all Zinc lozenges such as Cold-Eeze and zinc nose sprays that you can buy over the counter actually cause a temporary distortion in smelJ and taste especially in sweet sensations says Pelchat When you stop using them your nonnal senses of smell and taste usually return
Buckle up The single most common cause of a complete smell impairment Head injury like that sustained in a car accident says Hirsch Perhaps the easiest thing you can do to protect your senses of smell and taste is to always wear a seat belt while driving
Sid KJrchheimer last wrote for AARP The Magazine about scams (HRip-off Alert July-August 2004) He is also the author of a forthshycoming action guide that collects hundreds of tips on how to avoid conshysumer rip-offs (AARP BooksSterling spring 2006)
bull __tHdWtr~~
From AARP The Magazine SeptemberOctober 200S pp 24-27 Copyright 0 2005 by Sid Kirchheimer Reprinted by permission of the author
44
COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
o Describe the theories of hearing pitch and how we locate sounds
o Describe the nature and causes of hearing loss and describe the effects of noise on hearing and behavior What types of hearing and deafness problems currently exist What is the cochlear implant and what does it do c
o Describe our sense of smell (olfaction) and our sense of taste (gustation) Describe the relationship among taste smell and flavor~ Why does food taste so bland when I have a cold Is there a relationship between smell and memory Between smell and depression Between smell and illness Which is greater- smell or taste
o Describe the transduction process in the olfactory system Discuss the path that olfactory information follows to the brain
o What are pheromones Describe taste buds
o Describe the somatosensory systems which are spread throughout the body Describe the transduction process in the skin senses including touch pain and temperature What does the sense of touch provide
o What is kinesthesia and the vestibular sense What do they provide
o Describe the gate control theory of pain What are the bodys natural analgesics
o Discuss the effects ofsensory restriction
mtToductioa 10 Psycbl)log~ 201 Dr R()lIal~n ~[ Kln~
StJ)tlRY NOTES ON SENSATION (HAI~1)OUT)
Overview of the Humaa Senses
KiDelthia The sense UuglvtZ us information about the location of our body parts and allow our nOVen1elt
Vetibular Setlc Our SclSe ofbalance Viud SenciE ves) Our visual C3ll1cra or window of the world Sight for most pcoplc is be nos imPOrtlllt way of gathering imormation about the world Hurm (Audition) Is feing1t a distance Iniorms us of pressure cbanges in the world illat 7l1y talce place many meters away Physical movement is the stimulus for heariDg Tutc(Gustat1og) ActS as1 gatciceper ro the digestive system by providiDg imormaticn about the substance that may or may not be ingested SweD (Olfaction) Functioos as a distancc sense Provides information about chemic31s suspencied in the air Warns of impending danger as when we sniff escaping gas Plays a role in identifying other pcsoos Touch (Skin Scn~es) Pressure warmth C()ld and pain Enables us to detect what is acijacent to our bodies
Buic Concepts in Sensation
Senorv ReceptOr responsible tor coding iDIormatioo by converting or tansducng raw physicd energy into neurti impulses wbich are then interpreted by our ccnn nervous system T randuction the tramlation of physical energy into electrical signal Sonsorv Deprivation Ii condition mwhich m organism is deprived ot sensory stimulation P3vchophvsio the study of the reiatiooship between the physical narure of stimuli and a persalls sensory rczpooses to lhen
Absolute Threshold det=mining the smallest magnitllde of a stimulus that em be reliably discriminaIed from no stimulus at all 50 pcrccnt ofthc time Sifai-Detection Theorv amp thcory that addresses the role of psyehologica(and other factorS such as costS and benefits) in our ability to identify stimuli D~iding whether we have detected a given stimulus Having [0 rely on p~ decisioo criteria Sennrv Adapt2tioD the reductioo or disappearance ofsensory responsiveness that occurs when stimulation is unchanging or repetitious Difference Threshold or Just NoticubJe Difference (JNl) the minimum difference in intensity that a stimulus em be discriminated Weber Law amp law swing that the smallest detectable diffirence (JND) for myintlnsity of a stimulus is a coostant function of the intcosity of the stimulus This coostanl VariCl tOr C3Ch of the sensory sysums
Vision P311S o(tbe EYe Cornea rUlspannt shield that COVe3 the front of the tye
Lens focuses Iiyenht rays iaIling on the retina Bemis incoming light waves into oarrow rays Pupil opening in the center ofthe iris that helps regulacc the amount of light passing into the reU chamber of the eye Iris Controls the amoUllt ofliglll that cntCS the Ite Retina Is the neural tissue lining the inside back surlacc of the ey~ it absorbs light procsscs images and sends visual intomlauoo to the brain The brains envoy in the eye Contains the Rods aad Canes JaiIling black and white and color vision Optic Nerve a bundle oineunl fibes that eat out the back oithe Ie Cmy oeural imOnnaUon to the brain
Viual Disorder of the Retina Blind Spou occur due [0 a hole in the retinas optic disk You cmnot see the part of he image that falls cn tt Nursightedness fMyoDiah the inability to see objectS far away The eeball is too long so that light from distallt objects focus in front of the retina Farsightedness rHVlJernpia) inability to see objects close up The efebailis too short LigiJt focusC$ on l
lOint bchmd the retina
Page Two) S ummary-SelltioD
C1taracu 311 opague film mat grows over the lens Glaucoma degeneration of the opuc nerve caused by a pressUre buildup withio the yebail due to biockages thaI meet the drainage of the 3CqUeoUS humor Other Visual Disorders Diabetic retinopathy macular degeneration deached reMa
Viual Receptors Rods and Cone Rods 3l1d cones are the pilotorecepton in the reuna rllCY contam chemicals thaI absorb ligbt waves Rods middotAre specialized visual receptors that playa leey role in night vision and periphera vision middotOperate at low light intClSiti= and lead to achromatic (colorless) SClSations -Transmit sensations oilight and darlc only
-You depend on rods for visioll in dim light middotRods cm see only shades of black white and gray -Rods oumumbercones by about 120 million to 7 million -Rods contam lightscnsitive chemical Cllled Rhodopin a necessary clecicd to make Vitamin A A deficiency in both rcsults in night blindneSl Cone middotPlay in key role in daylight vision color vision and fine detail -Conccalrltcti most heavily in the ccntcr of the retina in an area called the fovea -Conuins J chemicals called Iodopins whicplusmn1 are necessary for color vision
Dark Adapration is the process of adapting from bright light to dim light Lizht Adaptation is the process of adapting from darlc to light
Theories ot Color Vision Trichromatic Theo Discovcnd thaI there are J primary colors blue green and red which can be misxcd to form aU other colors Proposes that the human eye has 3 types of receptors with diffmning sensitivities to diifcnnt wavelengths Our ability to peneive a secmingly unlimited array ofcolon results from thejoint action of the tree rcceptor types Our perception of ail colors are plOduced tbrcUyenh comobinations of activity by these 3 types of receptors
People who see a fWl range ofcolorr are ctlled rrich romatJ becmsc they register all J color clwmels Dichromau have only 2 color channels Monochromats are completely blind to diffcrexs in color
The Opponent-Process Theon The theory that color vision is made possible by 3 types of cones some of which respond to red or gnen Jight some to blue or yellow and some only to the intensity of light This theory suggestS thaI above the aeunJ level of the ntina we possess six kinds of cells that playa role in sensatioQS ofcolor Twe of these handle red and green 0= is stimulated by red light and inhibited by green light wberess the other is stimulated by green light and moiled by red IigilL This is why it is C3Iled an opponent-proc=s Two additional cells handle yellow and blue oae is stimulated by yellow light and inhibited by blue while the other shows the opposite pamm The remaining two rypes handle black and white qaU1 in m opponcm process llWlIler
HEARING -The process funcrion or power ofperceiving sound The stimuli for heuing or audition are sound waves - High and low sounds cm be distinguised by their pitch -The e3lis the structure through which we percive sound P3rtS oiilie eu include outer (visible part-funnes soundwaves into e3r cma1 that strikes the eItdrum) middle (includes the hammer anvil stirrup and OVU window) and inner (contains the auditory receptorsmiddot the cochlea and basilar mcnbrane)
Theories otHearinlo Pitch Ptace TheG f)t Pitch The piech of a sound is determined by the plac slong the basilarlIlCnbrane that vibraus in nsponse to it The bigher the pitch of soum the closer the nsponsive IlelfOQS lie to the oval window
Page Three) Summary-SensaciOD
Frequency Theon of Pitch Pilch perception depends on the stimulation of neural impulses that match the frequency of the sound waves DupUdty Theon Pitch perception depends both on tbeplacc and frequency oineural response
TYpa ot Hearinl Problemll
Conduetfon De_fnen Hearing loss caU$Cd by wax or injwy Sellllo[-Neural Deafne Loss caused by injwy to the hair cells or audjtory nerves Damage IS irreversible Stimulation DeafDen Deafness due to exposure to sounds that are exccsslvely loud Centra Dearness Caused by disease and tumors in the audilOry pathways and cortex of the brain Untreatablc
Cochlear Implant An artificial hearing device implanted in the skull Motion Slslmell Involves strlCtuns in the inner ear - the vestibular organs
Ioucb A number of diffennt skin sensatioas After the free nerve endings convert pressure warmth cold and paiD into nerve impulses these impulses ultimately reach the somatosensory area of the cortex At this point you experience the sensation of touch
lm A sigual that somcthiDg is wrong in the body Eadorphins act to reduce pain Gat Control Theory otPaln Involves the brain providing insttuctions to neurons to reie3Se endorphins and block pain in the body
Tate Tute is I chemical sense that responds to the chemical stl1ICtUre of substances Four basic tastes sweet salty sour bitta
SmeU The seme ofsmell is ten thousand times more sensitive than taste The firing ofneurons transmits information about odors to the brain via the olfactory bulb
Popular Studies re olfaction
Menstrual Svnchrony Psychologisc Martha McClintock monitored the menstrual cycles of 13Swomen and found that the cycles offtiends and roommates converged due to their spending time in close quarters
Pbernmones Produced by other members of the species and detected through the sense of smell Example animaLs marking territory Scents induce mating behavior
Dr ROSMYII M XlIIK ntrotblcdoll to Psycllology Article 8
F 7 cmr g RB
Sensational Thne-ups Fifteen ways to improve your vision hearing taste and sense of smell
SID KIRCHHEIMER
Are people around you mumbling more often these days Does food seem to need an extra splash of Tabasco to please the palate Would the newspaper be easier to read
if your arms were just a few feet longer and the print a bit bigger Welcome to the club By the time we hit middle age most of
us suffer from some decline of the senses But dont despair There are ways to protect-and even improve-your ability to see hear smell and taste all of lifes offerings Experts we conshysulted recommend the following senses-sharpening middotstrategies
Sight Only reading glasses or other special eyewear can foil the common cause of weakened vision presbyopia the so-called aging eyes that result when the lens of the eye loses its flexishybility making it harder to focus clearly on close objects But you can take measures to stave off some of the leading causes of age-related blindness See if these work for you
Pop five a day A National Eye Institute study shows that one of the best ways to arrest macular degeneration is by following a simple five-pill supplement regimen daily doses of500 mg of vishytamin C 400 intemational units of vitamin E 15 mg of beta carshyotene 80 mg of zinc oxide and 2 mg of cupric oxide You really need to take these in supplement form because there is no way you could get these amounts from food alone says National Eye mstitute researcher Emily Chew MD
Loosenup A study in the British Journal of Ophthalmology finds that a tight necktie may increase risk of glaucoma by conshystricting neck veins boosting fluid pressure inside the eyes to dangerous levels No one says you have to strangle yourself says study author Robert Ritch MD of the New York Eye and Ear Infirmary If you cant get your finger in between your neck and your collar easily its too tight
Keep your specs on The mainstay material in prescription eyewear-polycarbonate lenses-helps block harmful ultravishyolet light a key cause of cataracts says ophthalmologist Wilshyliam Uoyd MD of UC Davis Medical Center So keep your glasses on whenever youre outdoors (or don prescription sunshyglasses) And if youre 2020 look for nonprescription sunshy
glasses at the drugstore or mall that are labeled to protect against both UV A and UVB rays
Plow Into power plants Some of the disease-protecting chemicals naturaIly found in fruits and vegetables also shield these plants from UV rays and other environmental pollutants that can damage your vision While most types of produce are beneficial peas peppers and green leafy vegetables such as kale romaine lettuce and spinach stand out because theyre rich in lutein and other key vision-protecting nutrients
Get an early start Eye-harming environmental pollutantsshysmog in plain Englisb-are at their lowest levels early in the day To limit your exposure to toxins in the air Lloyd suggests doing yani work exercise and other outdoor activities early in the moming
Hearing While illness injury overuse of certain drugs and genetics can all lead to hearing loss the primary reason most aging Amerishycans go deaf is their past exposure to noise With every noise that is loud or long enough some of the 6000 or so tiny hairs inside each ear that allow sound waves to be heard are permashynently damaged causing a gradual hearing loss that becomes noticeable in middle age and beyond Some sound advice
Plug em Wearing ear protection is the obvious way to protect these sensitive hair ceUs but you dont have to look like an aipOl1 bagshygage handlerwhile doing it Small foam plugs that discreetly fit in your ear may actually be better than the bulky padded earmuff types says David Nielsen MD of the American Academy of OtolaryngologyshyHead and Neck Surgery These plugs reduce noise by about 20 decishybels compared with the 15-decibel protection you get from more exshypensive padded earmuffs Plus the plugs are cooler he points out
Work out In silence Regular exercise keeps hearing sharp by improving or maintaining good blood flow to the inner ear But during exercise when more blood is feeding muscles less may get to nerves that control hearing making them more vulnerable to noise-caused damage Some studies indicate that loud music or noise heard during exercise may be more damaging than noise heard at the same volumes when youre sedentary Researchers are not unanishymous about this but unless you need to listen to loud music while you exe~~ you probably shouldnt says Nielsen
43
ANNUAL EDIT10NS
Spark Your Sixth Sense
Just for fun we asked leading experts what can be done to maintain or enhance the sixth sense -abilities such as ESP telepathy and clairvoyance It turns out psychic abilities may actually benefit from aging Conditions that are more conducive for psychic experiences seem to ocshycur more readily in older people than in younger ones says researcher Emily Williams Kelly PhD of the Unishyversity of Virginias division of personality studies which studies psychic phenomena How better to get in touch with the other side Consider the following
bull Use the quiet When the house is absent of yelling kids blaring music and other immediate distractions youre more likely to be able to focus on the beyond These events seem to occur more readily in those who have them with quiet solitude and meditation says Kelly
bull Watch for signs People who are extroverted and open to the idea of having these experiences are more likely to show ESP abilities says Kelly And their glass is half fullft attitude includes taking clues from everyday events middotSigns are everywhere adds Lisa Nash a clairvoyant and online psychic reader at Global Psychic Inc Pay attention to what you see while you are driving It may be an indication of whats in your lifes path A dead deer on the side of the road might indicate that you are neglecting your inner power that comes from gentleness
bull Eat for illumination Nash says many psychics eat healthfully avoiding alcohol and drugs as well as
caffeine sugar and processed foods in order to maintain mental focus and clarity Meanwhile recent research shows that one of the omega-3 fatty acids found in heart-healthy fish such as salmon and mackerel can prevent age-related damage to a part of the brain where cells responsible for learning and memory communicate with one another -SK
Dont be a blowhard Strenuous nose blowing can cause temporary or pennanent hearing loss by rupturing the delicate structures inside the eardrum To relieve nasal congestion adshyvises Nielsen gently blow one nostril at a time
Get screened If you have diabetes youre more likely to suffer earlier and faster hearing loss probably because of impeded blood flow to nerves that control hearing If you have diabetes in particshyular you really should consider getting a yearly hearing test just as you get annual tests for vision kidney function and other possible dishyabetes complications says Nancy Vaughan PhD a researcher at the National Center for Rehabilitative Auditory Research in Portshyland Oregon who has investigated the diabetes-early-hearing-Ioss link Those with high blood pressure or high cholesterol could also benefit from regular hearing screenings she adds
Watch your aspirin Aspirin is among the 200 or so medicashytions that can cause hearing loss by damaging hearing hair cells
and nerves that carry sounds to the brain This is not to say you should ditch your daily aspirin therapy But it does mean you should be diligent about following the typical recommended dosages for heart health and pain--and not take much higher doses YoulI know youre taking too much aspirin if your ears ring but the ringing stops when you stop taking aspirin
Smell and Taste When smell is impaired an inability to taste usually follows This not only makes eating less pleasurable it can also lead to other problems Smell and taste get the digestive process rolling by triggering saliva and gastric juices to help digest food says Marcia Levin Pelchat PhD a scientist at Monell Chemical Senses Center in Philadelphia the nations leading institute for smell and taste research Before food is even eaten these senses allow the body to anticipate food and make absorpshytion more efficient And when you cant smell or taste food youre less likely to eat it risking malnutrition Chew over the following strategies for preserving the flavor in your life
Breathe in If youre sitting down for a hot meal says Alan Hirsch MD director of the Smell and Taste Treatment and Research Foundation in Chicago take advantage of the cool fact that its good to snifffood before you eat because heat aermiddot ates odor molecules that youll perceive as taste
Hit the showers A less practical but equally effective varishyation on the above principle The heat and humidity of a warm shower clears sinuses and helps dissolve molecules that facilishytate the ability to smell says Hirsch Plus youll be nice and clean for dinner
Manage your sniffles People with recurrent colds or allergy problems are more vulnerable to smell and taste impainnent feshycause they often develop nasal polyps that block the sense recepshytors inside the top of the nose Hirsch adds Its most noticeable while they have a cold or allergies but frequent nasal or sinus problems can lead to chronic problems in the ability to smell
But rethink that cold remedy A zinc deficiency is one suspected cause of smell problems but that doesnt mean cold remedies containing this nutrient are a cure-all Zinc lozenges such as Cold-Eeze and zinc nose sprays that you can buy over the counter actually cause a temporary distortion in smelJ and taste especially in sweet sensations says Pelchat When you stop using them your nonnal senses of smell and taste usually return
Buckle up The single most common cause of a complete smell impairment Head injury like that sustained in a car accident says Hirsch Perhaps the easiest thing you can do to protect your senses of smell and taste is to always wear a seat belt while driving
Sid KJrchheimer last wrote for AARP The Magazine about scams (HRip-off Alert July-August 2004) He is also the author of a forthshycoming action guide that collects hundreds of tips on how to avoid conshysumer rip-offs (AARP BooksSterling spring 2006)
bull __tHdWtr~~
From AARP The Magazine SeptemberOctober 200S pp 24-27 Copyright 0 2005 by Sid Kirchheimer Reprinted by permission of the author
44
COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
mtToductioa 10 Psycbl)log~ 201 Dr R()lIal~n ~[ Kln~
StJ)tlRY NOTES ON SENSATION (HAI~1)OUT)
Overview of the Humaa Senses
KiDelthia The sense UuglvtZ us information about the location of our body parts and allow our nOVen1elt
Vetibular Setlc Our SclSe ofbalance Viud SenciE ves) Our visual C3ll1cra or window of the world Sight for most pcoplc is be nos imPOrtlllt way of gathering imormation about the world Hurm (Audition) Is feing1t a distance Iniorms us of pressure cbanges in the world illat 7l1y talce place many meters away Physical movement is the stimulus for heariDg Tutc(Gustat1og) ActS as1 gatciceper ro the digestive system by providiDg imormaticn about the substance that may or may not be ingested SweD (Olfaction) Functioos as a distancc sense Provides information about chemic31s suspencied in the air Warns of impending danger as when we sniff escaping gas Plays a role in identifying other pcsoos Touch (Skin Scn~es) Pressure warmth C()ld and pain Enables us to detect what is acijacent to our bodies
Buic Concepts in Sensation
Senorv ReceptOr responsible tor coding iDIormatioo by converting or tansducng raw physicd energy into neurti impulses wbich are then interpreted by our ccnn nervous system T randuction the tramlation of physical energy into electrical signal Sonsorv Deprivation Ii condition mwhich m organism is deprived ot sensory stimulation P3vchophvsio the study of the reiatiooship between the physical narure of stimuli and a persalls sensory rczpooses to lhen
Absolute Threshold det=mining the smallest magnitllde of a stimulus that em be reliably discriminaIed from no stimulus at all 50 pcrccnt ofthc time Sifai-Detection Theorv amp thcory that addresses the role of psyehologica(and other factorS such as costS and benefits) in our ability to identify stimuli D~iding whether we have detected a given stimulus Having [0 rely on p~ decisioo criteria Sennrv Adapt2tioD the reductioo or disappearance ofsensory responsiveness that occurs when stimulation is unchanging or repetitious Difference Threshold or Just NoticubJe Difference (JNl) the minimum difference in intensity that a stimulus em be discriminated Weber Law amp law swing that the smallest detectable diffirence (JND) for myintlnsity of a stimulus is a coostant function of the intcosity of the stimulus This coostanl VariCl tOr C3Ch of the sensory sysums
Vision P311S o(tbe EYe Cornea rUlspannt shield that COVe3 the front of the tye
Lens focuses Iiyenht rays iaIling on the retina Bemis incoming light waves into oarrow rays Pupil opening in the center ofthe iris that helps regulacc the amount of light passing into the reU chamber of the eye Iris Controls the amoUllt ofliglll that cntCS the Ite Retina Is the neural tissue lining the inside back surlacc of the ey~ it absorbs light procsscs images and sends visual intomlauoo to the brain The brains envoy in the eye Contains the Rods aad Canes JaiIling black and white and color vision Optic Nerve a bundle oineunl fibes that eat out the back oithe Ie Cmy oeural imOnnaUon to the brain
Viual Disorder of the Retina Blind Spou occur due [0 a hole in the retinas optic disk You cmnot see the part of he image that falls cn tt Nursightedness fMyoDiah the inability to see objectS far away The eeball is too long so that light from distallt objects focus in front of the retina Farsightedness rHVlJernpia) inability to see objects close up The efebailis too short LigiJt focusC$ on l
lOint bchmd the retina
Page Two) S ummary-SelltioD
C1taracu 311 opague film mat grows over the lens Glaucoma degeneration of the opuc nerve caused by a pressUre buildup withio the yebail due to biockages thaI meet the drainage of the 3CqUeoUS humor Other Visual Disorders Diabetic retinopathy macular degeneration deached reMa
Viual Receptors Rods and Cone Rods 3l1d cones are the pilotorecepton in the reuna rllCY contam chemicals thaI absorb ligbt waves Rods middotAre specialized visual receptors that playa leey role in night vision and periphera vision middotOperate at low light intClSiti= and lead to achromatic (colorless) SClSations -Transmit sensations oilight and darlc only
-You depend on rods for visioll in dim light middotRods cm see only shades of black white and gray -Rods oumumbercones by about 120 million to 7 million -Rods contam lightscnsitive chemical Cllled Rhodopin a necessary clecicd to make Vitamin A A deficiency in both rcsults in night blindneSl Cone middotPlay in key role in daylight vision color vision and fine detail -Conccalrltcti most heavily in the ccntcr of the retina in an area called the fovea -Conuins J chemicals called Iodopins whicplusmn1 are necessary for color vision
Dark Adapration is the process of adapting from bright light to dim light Lizht Adaptation is the process of adapting from darlc to light
Theories ot Color Vision Trichromatic Theo Discovcnd thaI there are J primary colors blue green and red which can be misxcd to form aU other colors Proposes that the human eye has 3 types of receptors with diffmning sensitivities to diifcnnt wavelengths Our ability to peneive a secmingly unlimited array ofcolon results from thejoint action of the tree rcceptor types Our perception of ail colors are plOduced tbrcUyenh comobinations of activity by these 3 types of receptors
People who see a fWl range ofcolorr are ctlled rrich romatJ becmsc they register all J color clwmels Dichromau have only 2 color channels Monochromats are completely blind to diffcrexs in color
The Opponent-Process Theon The theory that color vision is made possible by 3 types of cones some of which respond to red or gnen Jight some to blue or yellow and some only to the intensity of light This theory suggestS thaI above the aeunJ level of the ntina we possess six kinds of cells that playa role in sensatioQS ofcolor Twe of these handle red and green 0= is stimulated by red light and inhibited by green light wberess the other is stimulated by green light and moiled by red IigilL This is why it is C3Iled an opponent-proc=s Two additional cells handle yellow and blue oae is stimulated by yellow light and inhibited by blue while the other shows the opposite pamm The remaining two rypes handle black and white qaU1 in m opponcm process llWlIler
HEARING -The process funcrion or power ofperceiving sound The stimuli for heuing or audition are sound waves - High and low sounds cm be distinguised by their pitch -The e3lis the structure through which we percive sound P3rtS oiilie eu include outer (visible part-funnes soundwaves into e3r cma1 that strikes the eItdrum) middle (includes the hammer anvil stirrup and OVU window) and inner (contains the auditory receptorsmiddot the cochlea and basilar mcnbrane)
Theories otHearinlo Pitch Ptace TheG f)t Pitch The piech of a sound is determined by the plac slong the basilarlIlCnbrane that vibraus in nsponse to it The bigher the pitch of soum the closer the nsponsive IlelfOQS lie to the oval window
Page Three) Summary-SensaciOD
Frequency Theon of Pitch Pilch perception depends on the stimulation of neural impulses that match the frequency of the sound waves DupUdty Theon Pitch perception depends both on tbeplacc and frequency oineural response
TYpa ot Hearinl Problemll
Conduetfon De_fnen Hearing loss caU$Cd by wax or injwy Sellllo[-Neural Deafne Loss caused by injwy to the hair cells or audjtory nerves Damage IS irreversible Stimulation DeafDen Deafness due to exposure to sounds that are exccsslvely loud Centra Dearness Caused by disease and tumors in the audilOry pathways and cortex of the brain Untreatablc
Cochlear Implant An artificial hearing device implanted in the skull Motion Slslmell Involves strlCtuns in the inner ear - the vestibular organs
Ioucb A number of diffennt skin sensatioas After the free nerve endings convert pressure warmth cold and paiD into nerve impulses these impulses ultimately reach the somatosensory area of the cortex At this point you experience the sensation of touch
lm A sigual that somcthiDg is wrong in the body Eadorphins act to reduce pain Gat Control Theory otPaln Involves the brain providing insttuctions to neurons to reie3Se endorphins and block pain in the body
Tate Tute is I chemical sense that responds to the chemical stl1ICtUre of substances Four basic tastes sweet salty sour bitta
SmeU The seme ofsmell is ten thousand times more sensitive than taste The firing ofneurons transmits information about odors to the brain via the olfactory bulb
Popular Studies re olfaction
Menstrual Svnchrony Psychologisc Martha McClintock monitored the menstrual cycles of 13Swomen and found that the cycles offtiends and roommates converged due to their spending time in close quarters
Pbernmones Produced by other members of the species and detected through the sense of smell Example animaLs marking territory Scents induce mating behavior
Dr ROSMYII M XlIIK ntrotblcdoll to Psycllology Article 8
F 7 cmr g RB
Sensational Thne-ups Fifteen ways to improve your vision hearing taste and sense of smell
SID KIRCHHEIMER
Are people around you mumbling more often these days Does food seem to need an extra splash of Tabasco to please the palate Would the newspaper be easier to read
if your arms were just a few feet longer and the print a bit bigger Welcome to the club By the time we hit middle age most of
us suffer from some decline of the senses But dont despair There are ways to protect-and even improve-your ability to see hear smell and taste all of lifes offerings Experts we conshysulted recommend the following senses-sharpening middotstrategies
Sight Only reading glasses or other special eyewear can foil the common cause of weakened vision presbyopia the so-called aging eyes that result when the lens of the eye loses its flexishybility making it harder to focus clearly on close objects But you can take measures to stave off some of the leading causes of age-related blindness See if these work for you
Pop five a day A National Eye Institute study shows that one of the best ways to arrest macular degeneration is by following a simple five-pill supplement regimen daily doses of500 mg of vishytamin C 400 intemational units of vitamin E 15 mg of beta carshyotene 80 mg of zinc oxide and 2 mg of cupric oxide You really need to take these in supplement form because there is no way you could get these amounts from food alone says National Eye mstitute researcher Emily Chew MD
Loosenup A study in the British Journal of Ophthalmology finds that a tight necktie may increase risk of glaucoma by conshystricting neck veins boosting fluid pressure inside the eyes to dangerous levels No one says you have to strangle yourself says study author Robert Ritch MD of the New York Eye and Ear Infirmary If you cant get your finger in between your neck and your collar easily its too tight
Keep your specs on The mainstay material in prescription eyewear-polycarbonate lenses-helps block harmful ultravishyolet light a key cause of cataracts says ophthalmologist Wilshyliam Uoyd MD of UC Davis Medical Center So keep your glasses on whenever youre outdoors (or don prescription sunshyglasses) And if youre 2020 look for nonprescription sunshy
glasses at the drugstore or mall that are labeled to protect against both UV A and UVB rays
Plow Into power plants Some of the disease-protecting chemicals naturaIly found in fruits and vegetables also shield these plants from UV rays and other environmental pollutants that can damage your vision While most types of produce are beneficial peas peppers and green leafy vegetables such as kale romaine lettuce and spinach stand out because theyre rich in lutein and other key vision-protecting nutrients
Get an early start Eye-harming environmental pollutantsshysmog in plain Englisb-are at their lowest levels early in the day To limit your exposure to toxins in the air Lloyd suggests doing yani work exercise and other outdoor activities early in the moming
Hearing While illness injury overuse of certain drugs and genetics can all lead to hearing loss the primary reason most aging Amerishycans go deaf is their past exposure to noise With every noise that is loud or long enough some of the 6000 or so tiny hairs inside each ear that allow sound waves to be heard are permashynently damaged causing a gradual hearing loss that becomes noticeable in middle age and beyond Some sound advice
Plug em Wearing ear protection is the obvious way to protect these sensitive hair ceUs but you dont have to look like an aipOl1 bagshygage handlerwhile doing it Small foam plugs that discreetly fit in your ear may actually be better than the bulky padded earmuff types says David Nielsen MD of the American Academy of OtolaryngologyshyHead and Neck Surgery These plugs reduce noise by about 20 decishybels compared with the 15-decibel protection you get from more exshypensive padded earmuffs Plus the plugs are cooler he points out
Work out In silence Regular exercise keeps hearing sharp by improving or maintaining good blood flow to the inner ear But during exercise when more blood is feeding muscles less may get to nerves that control hearing making them more vulnerable to noise-caused damage Some studies indicate that loud music or noise heard during exercise may be more damaging than noise heard at the same volumes when youre sedentary Researchers are not unanishymous about this but unless you need to listen to loud music while you exe~~ you probably shouldnt says Nielsen
43
ANNUAL EDIT10NS
Spark Your Sixth Sense
Just for fun we asked leading experts what can be done to maintain or enhance the sixth sense -abilities such as ESP telepathy and clairvoyance It turns out psychic abilities may actually benefit from aging Conditions that are more conducive for psychic experiences seem to ocshycur more readily in older people than in younger ones says researcher Emily Williams Kelly PhD of the Unishyversity of Virginias division of personality studies which studies psychic phenomena How better to get in touch with the other side Consider the following
bull Use the quiet When the house is absent of yelling kids blaring music and other immediate distractions youre more likely to be able to focus on the beyond These events seem to occur more readily in those who have them with quiet solitude and meditation says Kelly
bull Watch for signs People who are extroverted and open to the idea of having these experiences are more likely to show ESP abilities says Kelly And their glass is half fullft attitude includes taking clues from everyday events middotSigns are everywhere adds Lisa Nash a clairvoyant and online psychic reader at Global Psychic Inc Pay attention to what you see while you are driving It may be an indication of whats in your lifes path A dead deer on the side of the road might indicate that you are neglecting your inner power that comes from gentleness
bull Eat for illumination Nash says many psychics eat healthfully avoiding alcohol and drugs as well as
caffeine sugar and processed foods in order to maintain mental focus and clarity Meanwhile recent research shows that one of the omega-3 fatty acids found in heart-healthy fish such as salmon and mackerel can prevent age-related damage to a part of the brain where cells responsible for learning and memory communicate with one another -SK
Dont be a blowhard Strenuous nose blowing can cause temporary or pennanent hearing loss by rupturing the delicate structures inside the eardrum To relieve nasal congestion adshyvises Nielsen gently blow one nostril at a time
Get screened If you have diabetes youre more likely to suffer earlier and faster hearing loss probably because of impeded blood flow to nerves that control hearing If you have diabetes in particshyular you really should consider getting a yearly hearing test just as you get annual tests for vision kidney function and other possible dishyabetes complications says Nancy Vaughan PhD a researcher at the National Center for Rehabilitative Auditory Research in Portshyland Oregon who has investigated the diabetes-early-hearing-Ioss link Those with high blood pressure or high cholesterol could also benefit from regular hearing screenings she adds
Watch your aspirin Aspirin is among the 200 or so medicashytions that can cause hearing loss by damaging hearing hair cells
and nerves that carry sounds to the brain This is not to say you should ditch your daily aspirin therapy But it does mean you should be diligent about following the typical recommended dosages for heart health and pain--and not take much higher doses YoulI know youre taking too much aspirin if your ears ring but the ringing stops when you stop taking aspirin
Smell and Taste When smell is impaired an inability to taste usually follows This not only makes eating less pleasurable it can also lead to other problems Smell and taste get the digestive process rolling by triggering saliva and gastric juices to help digest food says Marcia Levin Pelchat PhD a scientist at Monell Chemical Senses Center in Philadelphia the nations leading institute for smell and taste research Before food is even eaten these senses allow the body to anticipate food and make absorpshytion more efficient And when you cant smell or taste food youre less likely to eat it risking malnutrition Chew over the following strategies for preserving the flavor in your life
Breathe in If youre sitting down for a hot meal says Alan Hirsch MD director of the Smell and Taste Treatment and Research Foundation in Chicago take advantage of the cool fact that its good to snifffood before you eat because heat aermiddot ates odor molecules that youll perceive as taste
Hit the showers A less practical but equally effective varishyation on the above principle The heat and humidity of a warm shower clears sinuses and helps dissolve molecules that facilishytate the ability to smell says Hirsch Plus youll be nice and clean for dinner
Manage your sniffles People with recurrent colds or allergy problems are more vulnerable to smell and taste impainnent feshycause they often develop nasal polyps that block the sense recepshytors inside the top of the nose Hirsch adds Its most noticeable while they have a cold or allergies but frequent nasal or sinus problems can lead to chronic problems in the ability to smell
But rethink that cold remedy A zinc deficiency is one suspected cause of smell problems but that doesnt mean cold remedies containing this nutrient are a cure-all Zinc lozenges such as Cold-Eeze and zinc nose sprays that you can buy over the counter actually cause a temporary distortion in smelJ and taste especially in sweet sensations says Pelchat When you stop using them your nonnal senses of smell and taste usually return
Buckle up The single most common cause of a complete smell impairment Head injury like that sustained in a car accident says Hirsch Perhaps the easiest thing you can do to protect your senses of smell and taste is to always wear a seat belt while driving
Sid KJrchheimer last wrote for AARP The Magazine about scams (HRip-off Alert July-August 2004) He is also the author of a forthshycoming action guide that collects hundreds of tips on how to avoid conshysumer rip-offs (AARP BooksSterling spring 2006)
bull __tHdWtr~~
From AARP The Magazine SeptemberOctober 200S pp 24-27 Copyright 0 2005 by Sid Kirchheimer Reprinted by permission of the author
44
COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
Page Two) S ummary-SelltioD
C1taracu 311 opague film mat grows over the lens Glaucoma degeneration of the opuc nerve caused by a pressUre buildup withio the yebail due to biockages thaI meet the drainage of the 3CqUeoUS humor Other Visual Disorders Diabetic retinopathy macular degeneration deached reMa
Viual Receptors Rods and Cone Rods 3l1d cones are the pilotorecepton in the reuna rllCY contam chemicals thaI absorb ligbt waves Rods middotAre specialized visual receptors that playa leey role in night vision and periphera vision middotOperate at low light intClSiti= and lead to achromatic (colorless) SClSations -Transmit sensations oilight and darlc only
-You depend on rods for visioll in dim light middotRods cm see only shades of black white and gray -Rods oumumbercones by about 120 million to 7 million -Rods contam lightscnsitive chemical Cllled Rhodopin a necessary clecicd to make Vitamin A A deficiency in both rcsults in night blindneSl Cone middotPlay in key role in daylight vision color vision and fine detail -Conccalrltcti most heavily in the ccntcr of the retina in an area called the fovea -Conuins J chemicals called Iodopins whicplusmn1 are necessary for color vision
Dark Adapration is the process of adapting from bright light to dim light Lizht Adaptation is the process of adapting from darlc to light
Theories ot Color Vision Trichromatic Theo Discovcnd thaI there are J primary colors blue green and red which can be misxcd to form aU other colors Proposes that the human eye has 3 types of receptors with diffmning sensitivities to diifcnnt wavelengths Our ability to peneive a secmingly unlimited array ofcolon results from thejoint action of the tree rcceptor types Our perception of ail colors are plOduced tbrcUyenh comobinations of activity by these 3 types of receptors
People who see a fWl range ofcolorr are ctlled rrich romatJ becmsc they register all J color clwmels Dichromau have only 2 color channels Monochromats are completely blind to diffcrexs in color
The Opponent-Process Theon The theory that color vision is made possible by 3 types of cones some of which respond to red or gnen Jight some to blue or yellow and some only to the intensity of light This theory suggestS thaI above the aeunJ level of the ntina we possess six kinds of cells that playa role in sensatioQS ofcolor Twe of these handle red and green 0= is stimulated by red light and inhibited by green light wberess the other is stimulated by green light and moiled by red IigilL This is why it is C3Iled an opponent-proc=s Two additional cells handle yellow and blue oae is stimulated by yellow light and inhibited by blue while the other shows the opposite pamm The remaining two rypes handle black and white qaU1 in m opponcm process llWlIler
HEARING -The process funcrion or power ofperceiving sound The stimuli for heuing or audition are sound waves - High and low sounds cm be distinguised by their pitch -The e3lis the structure through which we percive sound P3rtS oiilie eu include outer (visible part-funnes soundwaves into e3r cma1 that strikes the eItdrum) middle (includes the hammer anvil stirrup and OVU window) and inner (contains the auditory receptorsmiddot the cochlea and basilar mcnbrane)
Theories otHearinlo Pitch Ptace TheG f)t Pitch The piech of a sound is determined by the plac slong the basilarlIlCnbrane that vibraus in nsponse to it The bigher the pitch of soum the closer the nsponsive IlelfOQS lie to the oval window
Page Three) Summary-SensaciOD
Frequency Theon of Pitch Pilch perception depends on the stimulation of neural impulses that match the frequency of the sound waves DupUdty Theon Pitch perception depends both on tbeplacc and frequency oineural response
TYpa ot Hearinl Problemll
Conduetfon De_fnen Hearing loss caU$Cd by wax or injwy Sellllo[-Neural Deafne Loss caused by injwy to the hair cells or audjtory nerves Damage IS irreversible Stimulation DeafDen Deafness due to exposure to sounds that are exccsslvely loud Centra Dearness Caused by disease and tumors in the audilOry pathways and cortex of the brain Untreatablc
Cochlear Implant An artificial hearing device implanted in the skull Motion Slslmell Involves strlCtuns in the inner ear - the vestibular organs
Ioucb A number of diffennt skin sensatioas After the free nerve endings convert pressure warmth cold and paiD into nerve impulses these impulses ultimately reach the somatosensory area of the cortex At this point you experience the sensation of touch
lm A sigual that somcthiDg is wrong in the body Eadorphins act to reduce pain Gat Control Theory otPaln Involves the brain providing insttuctions to neurons to reie3Se endorphins and block pain in the body
Tate Tute is I chemical sense that responds to the chemical stl1ICtUre of substances Four basic tastes sweet salty sour bitta
SmeU The seme ofsmell is ten thousand times more sensitive than taste The firing ofneurons transmits information about odors to the brain via the olfactory bulb
Popular Studies re olfaction
Menstrual Svnchrony Psychologisc Martha McClintock monitored the menstrual cycles of 13Swomen and found that the cycles offtiends and roommates converged due to their spending time in close quarters
Pbernmones Produced by other members of the species and detected through the sense of smell Example animaLs marking territory Scents induce mating behavior
Dr ROSMYII M XlIIK ntrotblcdoll to Psycllology Article 8
F 7 cmr g RB
Sensational Thne-ups Fifteen ways to improve your vision hearing taste and sense of smell
SID KIRCHHEIMER
Are people around you mumbling more often these days Does food seem to need an extra splash of Tabasco to please the palate Would the newspaper be easier to read
if your arms were just a few feet longer and the print a bit bigger Welcome to the club By the time we hit middle age most of
us suffer from some decline of the senses But dont despair There are ways to protect-and even improve-your ability to see hear smell and taste all of lifes offerings Experts we conshysulted recommend the following senses-sharpening middotstrategies
Sight Only reading glasses or other special eyewear can foil the common cause of weakened vision presbyopia the so-called aging eyes that result when the lens of the eye loses its flexishybility making it harder to focus clearly on close objects But you can take measures to stave off some of the leading causes of age-related blindness See if these work for you
Pop five a day A National Eye Institute study shows that one of the best ways to arrest macular degeneration is by following a simple five-pill supplement regimen daily doses of500 mg of vishytamin C 400 intemational units of vitamin E 15 mg of beta carshyotene 80 mg of zinc oxide and 2 mg of cupric oxide You really need to take these in supplement form because there is no way you could get these amounts from food alone says National Eye mstitute researcher Emily Chew MD
Loosenup A study in the British Journal of Ophthalmology finds that a tight necktie may increase risk of glaucoma by conshystricting neck veins boosting fluid pressure inside the eyes to dangerous levels No one says you have to strangle yourself says study author Robert Ritch MD of the New York Eye and Ear Infirmary If you cant get your finger in between your neck and your collar easily its too tight
Keep your specs on The mainstay material in prescription eyewear-polycarbonate lenses-helps block harmful ultravishyolet light a key cause of cataracts says ophthalmologist Wilshyliam Uoyd MD of UC Davis Medical Center So keep your glasses on whenever youre outdoors (or don prescription sunshyglasses) And if youre 2020 look for nonprescription sunshy
glasses at the drugstore or mall that are labeled to protect against both UV A and UVB rays
Plow Into power plants Some of the disease-protecting chemicals naturaIly found in fruits and vegetables also shield these plants from UV rays and other environmental pollutants that can damage your vision While most types of produce are beneficial peas peppers and green leafy vegetables such as kale romaine lettuce and spinach stand out because theyre rich in lutein and other key vision-protecting nutrients
Get an early start Eye-harming environmental pollutantsshysmog in plain Englisb-are at their lowest levels early in the day To limit your exposure to toxins in the air Lloyd suggests doing yani work exercise and other outdoor activities early in the moming
Hearing While illness injury overuse of certain drugs and genetics can all lead to hearing loss the primary reason most aging Amerishycans go deaf is their past exposure to noise With every noise that is loud or long enough some of the 6000 or so tiny hairs inside each ear that allow sound waves to be heard are permashynently damaged causing a gradual hearing loss that becomes noticeable in middle age and beyond Some sound advice
Plug em Wearing ear protection is the obvious way to protect these sensitive hair ceUs but you dont have to look like an aipOl1 bagshygage handlerwhile doing it Small foam plugs that discreetly fit in your ear may actually be better than the bulky padded earmuff types says David Nielsen MD of the American Academy of OtolaryngologyshyHead and Neck Surgery These plugs reduce noise by about 20 decishybels compared with the 15-decibel protection you get from more exshypensive padded earmuffs Plus the plugs are cooler he points out
Work out In silence Regular exercise keeps hearing sharp by improving or maintaining good blood flow to the inner ear But during exercise when more blood is feeding muscles less may get to nerves that control hearing making them more vulnerable to noise-caused damage Some studies indicate that loud music or noise heard during exercise may be more damaging than noise heard at the same volumes when youre sedentary Researchers are not unanishymous about this but unless you need to listen to loud music while you exe~~ you probably shouldnt says Nielsen
43
ANNUAL EDIT10NS
Spark Your Sixth Sense
Just for fun we asked leading experts what can be done to maintain or enhance the sixth sense -abilities such as ESP telepathy and clairvoyance It turns out psychic abilities may actually benefit from aging Conditions that are more conducive for psychic experiences seem to ocshycur more readily in older people than in younger ones says researcher Emily Williams Kelly PhD of the Unishyversity of Virginias division of personality studies which studies psychic phenomena How better to get in touch with the other side Consider the following
bull Use the quiet When the house is absent of yelling kids blaring music and other immediate distractions youre more likely to be able to focus on the beyond These events seem to occur more readily in those who have them with quiet solitude and meditation says Kelly
bull Watch for signs People who are extroverted and open to the idea of having these experiences are more likely to show ESP abilities says Kelly And their glass is half fullft attitude includes taking clues from everyday events middotSigns are everywhere adds Lisa Nash a clairvoyant and online psychic reader at Global Psychic Inc Pay attention to what you see while you are driving It may be an indication of whats in your lifes path A dead deer on the side of the road might indicate that you are neglecting your inner power that comes from gentleness
bull Eat for illumination Nash says many psychics eat healthfully avoiding alcohol and drugs as well as
caffeine sugar and processed foods in order to maintain mental focus and clarity Meanwhile recent research shows that one of the omega-3 fatty acids found in heart-healthy fish such as salmon and mackerel can prevent age-related damage to a part of the brain where cells responsible for learning and memory communicate with one another -SK
Dont be a blowhard Strenuous nose blowing can cause temporary or pennanent hearing loss by rupturing the delicate structures inside the eardrum To relieve nasal congestion adshyvises Nielsen gently blow one nostril at a time
Get screened If you have diabetes youre more likely to suffer earlier and faster hearing loss probably because of impeded blood flow to nerves that control hearing If you have diabetes in particshyular you really should consider getting a yearly hearing test just as you get annual tests for vision kidney function and other possible dishyabetes complications says Nancy Vaughan PhD a researcher at the National Center for Rehabilitative Auditory Research in Portshyland Oregon who has investigated the diabetes-early-hearing-Ioss link Those with high blood pressure or high cholesterol could also benefit from regular hearing screenings she adds
Watch your aspirin Aspirin is among the 200 or so medicashytions that can cause hearing loss by damaging hearing hair cells
and nerves that carry sounds to the brain This is not to say you should ditch your daily aspirin therapy But it does mean you should be diligent about following the typical recommended dosages for heart health and pain--and not take much higher doses YoulI know youre taking too much aspirin if your ears ring but the ringing stops when you stop taking aspirin
Smell and Taste When smell is impaired an inability to taste usually follows This not only makes eating less pleasurable it can also lead to other problems Smell and taste get the digestive process rolling by triggering saliva and gastric juices to help digest food says Marcia Levin Pelchat PhD a scientist at Monell Chemical Senses Center in Philadelphia the nations leading institute for smell and taste research Before food is even eaten these senses allow the body to anticipate food and make absorpshytion more efficient And when you cant smell or taste food youre less likely to eat it risking malnutrition Chew over the following strategies for preserving the flavor in your life
Breathe in If youre sitting down for a hot meal says Alan Hirsch MD director of the Smell and Taste Treatment and Research Foundation in Chicago take advantage of the cool fact that its good to snifffood before you eat because heat aermiddot ates odor molecules that youll perceive as taste
Hit the showers A less practical but equally effective varishyation on the above principle The heat and humidity of a warm shower clears sinuses and helps dissolve molecules that facilishytate the ability to smell says Hirsch Plus youll be nice and clean for dinner
Manage your sniffles People with recurrent colds or allergy problems are more vulnerable to smell and taste impainnent feshycause they often develop nasal polyps that block the sense recepshytors inside the top of the nose Hirsch adds Its most noticeable while they have a cold or allergies but frequent nasal or sinus problems can lead to chronic problems in the ability to smell
But rethink that cold remedy A zinc deficiency is one suspected cause of smell problems but that doesnt mean cold remedies containing this nutrient are a cure-all Zinc lozenges such as Cold-Eeze and zinc nose sprays that you can buy over the counter actually cause a temporary distortion in smelJ and taste especially in sweet sensations says Pelchat When you stop using them your nonnal senses of smell and taste usually return
Buckle up The single most common cause of a complete smell impairment Head injury like that sustained in a car accident says Hirsch Perhaps the easiest thing you can do to protect your senses of smell and taste is to always wear a seat belt while driving
Sid KJrchheimer last wrote for AARP The Magazine about scams (HRip-off Alert July-August 2004) He is also the author of a forthshycoming action guide that collects hundreds of tips on how to avoid conshysumer rip-offs (AARP BooksSterling spring 2006)
bull __tHdWtr~~
From AARP The Magazine SeptemberOctober 200S pp 24-27 Copyright 0 2005 by Sid Kirchheimer Reprinted by permission of the author
44
COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
Page Three) Summary-SensaciOD
Frequency Theon of Pitch Pilch perception depends on the stimulation of neural impulses that match the frequency of the sound waves DupUdty Theon Pitch perception depends both on tbeplacc and frequency oineural response
TYpa ot Hearinl Problemll
Conduetfon De_fnen Hearing loss caU$Cd by wax or injwy Sellllo[-Neural Deafne Loss caused by injwy to the hair cells or audjtory nerves Damage IS irreversible Stimulation DeafDen Deafness due to exposure to sounds that are exccsslvely loud Centra Dearness Caused by disease and tumors in the audilOry pathways and cortex of the brain Untreatablc
Cochlear Implant An artificial hearing device implanted in the skull Motion Slslmell Involves strlCtuns in the inner ear - the vestibular organs
Ioucb A number of diffennt skin sensatioas After the free nerve endings convert pressure warmth cold and paiD into nerve impulses these impulses ultimately reach the somatosensory area of the cortex At this point you experience the sensation of touch
lm A sigual that somcthiDg is wrong in the body Eadorphins act to reduce pain Gat Control Theory otPaln Involves the brain providing insttuctions to neurons to reie3Se endorphins and block pain in the body
Tate Tute is I chemical sense that responds to the chemical stl1ICtUre of substances Four basic tastes sweet salty sour bitta
SmeU The seme ofsmell is ten thousand times more sensitive than taste The firing ofneurons transmits information about odors to the brain via the olfactory bulb
Popular Studies re olfaction
Menstrual Svnchrony Psychologisc Martha McClintock monitored the menstrual cycles of 13Swomen and found that the cycles offtiends and roommates converged due to their spending time in close quarters
Pbernmones Produced by other members of the species and detected through the sense of smell Example animaLs marking territory Scents induce mating behavior
Dr ROSMYII M XlIIK ntrotblcdoll to Psycllology Article 8
F 7 cmr g RB
Sensational Thne-ups Fifteen ways to improve your vision hearing taste and sense of smell
SID KIRCHHEIMER
Are people around you mumbling more often these days Does food seem to need an extra splash of Tabasco to please the palate Would the newspaper be easier to read
if your arms were just a few feet longer and the print a bit bigger Welcome to the club By the time we hit middle age most of
us suffer from some decline of the senses But dont despair There are ways to protect-and even improve-your ability to see hear smell and taste all of lifes offerings Experts we conshysulted recommend the following senses-sharpening middotstrategies
Sight Only reading glasses or other special eyewear can foil the common cause of weakened vision presbyopia the so-called aging eyes that result when the lens of the eye loses its flexishybility making it harder to focus clearly on close objects But you can take measures to stave off some of the leading causes of age-related blindness See if these work for you
Pop five a day A National Eye Institute study shows that one of the best ways to arrest macular degeneration is by following a simple five-pill supplement regimen daily doses of500 mg of vishytamin C 400 intemational units of vitamin E 15 mg of beta carshyotene 80 mg of zinc oxide and 2 mg of cupric oxide You really need to take these in supplement form because there is no way you could get these amounts from food alone says National Eye mstitute researcher Emily Chew MD
Loosenup A study in the British Journal of Ophthalmology finds that a tight necktie may increase risk of glaucoma by conshystricting neck veins boosting fluid pressure inside the eyes to dangerous levels No one says you have to strangle yourself says study author Robert Ritch MD of the New York Eye and Ear Infirmary If you cant get your finger in between your neck and your collar easily its too tight
Keep your specs on The mainstay material in prescription eyewear-polycarbonate lenses-helps block harmful ultravishyolet light a key cause of cataracts says ophthalmologist Wilshyliam Uoyd MD of UC Davis Medical Center So keep your glasses on whenever youre outdoors (or don prescription sunshyglasses) And if youre 2020 look for nonprescription sunshy
glasses at the drugstore or mall that are labeled to protect against both UV A and UVB rays
Plow Into power plants Some of the disease-protecting chemicals naturaIly found in fruits and vegetables also shield these plants from UV rays and other environmental pollutants that can damage your vision While most types of produce are beneficial peas peppers and green leafy vegetables such as kale romaine lettuce and spinach stand out because theyre rich in lutein and other key vision-protecting nutrients
Get an early start Eye-harming environmental pollutantsshysmog in plain Englisb-are at their lowest levels early in the day To limit your exposure to toxins in the air Lloyd suggests doing yani work exercise and other outdoor activities early in the moming
Hearing While illness injury overuse of certain drugs and genetics can all lead to hearing loss the primary reason most aging Amerishycans go deaf is their past exposure to noise With every noise that is loud or long enough some of the 6000 or so tiny hairs inside each ear that allow sound waves to be heard are permashynently damaged causing a gradual hearing loss that becomes noticeable in middle age and beyond Some sound advice
Plug em Wearing ear protection is the obvious way to protect these sensitive hair ceUs but you dont have to look like an aipOl1 bagshygage handlerwhile doing it Small foam plugs that discreetly fit in your ear may actually be better than the bulky padded earmuff types says David Nielsen MD of the American Academy of OtolaryngologyshyHead and Neck Surgery These plugs reduce noise by about 20 decishybels compared with the 15-decibel protection you get from more exshypensive padded earmuffs Plus the plugs are cooler he points out
Work out In silence Regular exercise keeps hearing sharp by improving or maintaining good blood flow to the inner ear But during exercise when more blood is feeding muscles less may get to nerves that control hearing making them more vulnerable to noise-caused damage Some studies indicate that loud music or noise heard during exercise may be more damaging than noise heard at the same volumes when youre sedentary Researchers are not unanishymous about this but unless you need to listen to loud music while you exe~~ you probably shouldnt says Nielsen
43
ANNUAL EDIT10NS
Spark Your Sixth Sense
Just for fun we asked leading experts what can be done to maintain or enhance the sixth sense -abilities such as ESP telepathy and clairvoyance It turns out psychic abilities may actually benefit from aging Conditions that are more conducive for psychic experiences seem to ocshycur more readily in older people than in younger ones says researcher Emily Williams Kelly PhD of the Unishyversity of Virginias division of personality studies which studies psychic phenomena How better to get in touch with the other side Consider the following
bull Use the quiet When the house is absent of yelling kids blaring music and other immediate distractions youre more likely to be able to focus on the beyond These events seem to occur more readily in those who have them with quiet solitude and meditation says Kelly
bull Watch for signs People who are extroverted and open to the idea of having these experiences are more likely to show ESP abilities says Kelly And their glass is half fullft attitude includes taking clues from everyday events middotSigns are everywhere adds Lisa Nash a clairvoyant and online psychic reader at Global Psychic Inc Pay attention to what you see while you are driving It may be an indication of whats in your lifes path A dead deer on the side of the road might indicate that you are neglecting your inner power that comes from gentleness
bull Eat for illumination Nash says many psychics eat healthfully avoiding alcohol and drugs as well as
caffeine sugar and processed foods in order to maintain mental focus and clarity Meanwhile recent research shows that one of the omega-3 fatty acids found in heart-healthy fish such as salmon and mackerel can prevent age-related damage to a part of the brain where cells responsible for learning and memory communicate with one another -SK
Dont be a blowhard Strenuous nose blowing can cause temporary or pennanent hearing loss by rupturing the delicate structures inside the eardrum To relieve nasal congestion adshyvises Nielsen gently blow one nostril at a time
Get screened If you have diabetes youre more likely to suffer earlier and faster hearing loss probably because of impeded blood flow to nerves that control hearing If you have diabetes in particshyular you really should consider getting a yearly hearing test just as you get annual tests for vision kidney function and other possible dishyabetes complications says Nancy Vaughan PhD a researcher at the National Center for Rehabilitative Auditory Research in Portshyland Oregon who has investigated the diabetes-early-hearing-Ioss link Those with high blood pressure or high cholesterol could also benefit from regular hearing screenings she adds
Watch your aspirin Aspirin is among the 200 or so medicashytions that can cause hearing loss by damaging hearing hair cells
and nerves that carry sounds to the brain This is not to say you should ditch your daily aspirin therapy But it does mean you should be diligent about following the typical recommended dosages for heart health and pain--and not take much higher doses YoulI know youre taking too much aspirin if your ears ring but the ringing stops when you stop taking aspirin
Smell and Taste When smell is impaired an inability to taste usually follows This not only makes eating less pleasurable it can also lead to other problems Smell and taste get the digestive process rolling by triggering saliva and gastric juices to help digest food says Marcia Levin Pelchat PhD a scientist at Monell Chemical Senses Center in Philadelphia the nations leading institute for smell and taste research Before food is even eaten these senses allow the body to anticipate food and make absorpshytion more efficient And when you cant smell or taste food youre less likely to eat it risking malnutrition Chew over the following strategies for preserving the flavor in your life
Breathe in If youre sitting down for a hot meal says Alan Hirsch MD director of the Smell and Taste Treatment and Research Foundation in Chicago take advantage of the cool fact that its good to snifffood before you eat because heat aermiddot ates odor molecules that youll perceive as taste
Hit the showers A less practical but equally effective varishyation on the above principle The heat and humidity of a warm shower clears sinuses and helps dissolve molecules that facilishytate the ability to smell says Hirsch Plus youll be nice and clean for dinner
Manage your sniffles People with recurrent colds or allergy problems are more vulnerable to smell and taste impainnent feshycause they often develop nasal polyps that block the sense recepshytors inside the top of the nose Hirsch adds Its most noticeable while they have a cold or allergies but frequent nasal or sinus problems can lead to chronic problems in the ability to smell
But rethink that cold remedy A zinc deficiency is one suspected cause of smell problems but that doesnt mean cold remedies containing this nutrient are a cure-all Zinc lozenges such as Cold-Eeze and zinc nose sprays that you can buy over the counter actually cause a temporary distortion in smelJ and taste especially in sweet sensations says Pelchat When you stop using them your nonnal senses of smell and taste usually return
Buckle up The single most common cause of a complete smell impairment Head injury like that sustained in a car accident says Hirsch Perhaps the easiest thing you can do to protect your senses of smell and taste is to always wear a seat belt while driving
Sid KJrchheimer last wrote for AARP The Magazine about scams (HRip-off Alert July-August 2004) He is also the author of a forthshycoming action guide that collects hundreds of tips on how to avoid conshysumer rip-offs (AARP BooksSterling spring 2006)
bull __tHdWtr~~
From AARP The Magazine SeptemberOctober 200S pp 24-27 Copyright 0 2005 by Sid Kirchheimer Reprinted by permission of the author
44
COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
Dr ROSMYII M XlIIK ntrotblcdoll to Psycllology Article 8
F 7 cmr g RB
Sensational Thne-ups Fifteen ways to improve your vision hearing taste and sense of smell
SID KIRCHHEIMER
Are people around you mumbling more often these days Does food seem to need an extra splash of Tabasco to please the palate Would the newspaper be easier to read
if your arms were just a few feet longer and the print a bit bigger Welcome to the club By the time we hit middle age most of
us suffer from some decline of the senses But dont despair There are ways to protect-and even improve-your ability to see hear smell and taste all of lifes offerings Experts we conshysulted recommend the following senses-sharpening middotstrategies
Sight Only reading glasses or other special eyewear can foil the common cause of weakened vision presbyopia the so-called aging eyes that result when the lens of the eye loses its flexishybility making it harder to focus clearly on close objects But you can take measures to stave off some of the leading causes of age-related blindness See if these work for you
Pop five a day A National Eye Institute study shows that one of the best ways to arrest macular degeneration is by following a simple five-pill supplement regimen daily doses of500 mg of vishytamin C 400 intemational units of vitamin E 15 mg of beta carshyotene 80 mg of zinc oxide and 2 mg of cupric oxide You really need to take these in supplement form because there is no way you could get these amounts from food alone says National Eye mstitute researcher Emily Chew MD
Loosenup A study in the British Journal of Ophthalmology finds that a tight necktie may increase risk of glaucoma by conshystricting neck veins boosting fluid pressure inside the eyes to dangerous levels No one says you have to strangle yourself says study author Robert Ritch MD of the New York Eye and Ear Infirmary If you cant get your finger in between your neck and your collar easily its too tight
Keep your specs on The mainstay material in prescription eyewear-polycarbonate lenses-helps block harmful ultravishyolet light a key cause of cataracts says ophthalmologist Wilshyliam Uoyd MD of UC Davis Medical Center So keep your glasses on whenever youre outdoors (or don prescription sunshyglasses) And if youre 2020 look for nonprescription sunshy
glasses at the drugstore or mall that are labeled to protect against both UV A and UVB rays
Plow Into power plants Some of the disease-protecting chemicals naturaIly found in fruits and vegetables also shield these plants from UV rays and other environmental pollutants that can damage your vision While most types of produce are beneficial peas peppers and green leafy vegetables such as kale romaine lettuce and spinach stand out because theyre rich in lutein and other key vision-protecting nutrients
Get an early start Eye-harming environmental pollutantsshysmog in plain Englisb-are at their lowest levels early in the day To limit your exposure to toxins in the air Lloyd suggests doing yani work exercise and other outdoor activities early in the moming
Hearing While illness injury overuse of certain drugs and genetics can all lead to hearing loss the primary reason most aging Amerishycans go deaf is their past exposure to noise With every noise that is loud or long enough some of the 6000 or so tiny hairs inside each ear that allow sound waves to be heard are permashynently damaged causing a gradual hearing loss that becomes noticeable in middle age and beyond Some sound advice
Plug em Wearing ear protection is the obvious way to protect these sensitive hair ceUs but you dont have to look like an aipOl1 bagshygage handlerwhile doing it Small foam plugs that discreetly fit in your ear may actually be better than the bulky padded earmuff types says David Nielsen MD of the American Academy of OtolaryngologyshyHead and Neck Surgery These plugs reduce noise by about 20 decishybels compared with the 15-decibel protection you get from more exshypensive padded earmuffs Plus the plugs are cooler he points out
Work out In silence Regular exercise keeps hearing sharp by improving or maintaining good blood flow to the inner ear But during exercise when more blood is feeding muscles less may get to nerves that control hearing making them more vulnerable to noise-caused damage Some studies indicate that loud music or noise heard during exercise may be more damaging than noise heard at the same volumes when youre sedentary Researchers are not unanishymous about this but unless you need to listen to loud music while you exe~~ you probably shouldnt says Nielsen
43
ANNUAL EDIT10NS
Spark Your Sixth Sense
Just for fun we asked leading experts what can be done to maintain or enhance the sixth sense -abilities such as ESP telepathy and clairvoyance It turns out psychic abilities may actually benefit from aging Conditions that are more conducive for psychic experiences seem to ocshycur more readily in older people than in younger ones says researcher Emily Williams Kelly PhD of the Unishyversity of Virginias division of personality studies which studies psychic phenomena How better to get in touch with the other side Consider the following
bull Use the quiet When the house is absent of yelling kids blaring music and other immediate distractions youre more likely to be able to focus on the beyond These events seem to occur more readily in those who have them with quiet solitude and meditation says Kelly
bull Watch for signs People who are extroverted and open to the idea of having these experiences are more likely to show ESP abilities says Kelly And their glass is half fullft attitude includes taking clues from everyday events middotSigns are everywhere adds Lisa Nash a clairvoyant and online psychic reader at Global Psychic Inc Pay attention to what you see while you are driving It may be an indication of whats in your lifes path A dead deer on the side of the road might indicate that you are neglecting your inner power that comes from gentleness
bull Eat for illumination Nash says many psychics eat healthfully avoiding alcohol and drugs as well as
caffeine sugar and processed foods in order to maintain mental focus and clarity Meanwhile recent research shows that one of the omega-3 fatty acids found in heart-healthy fish such as salmon and mackerel can prevent age-related damage to a part of the brain where cells responsible for learning and memory communicate with one another -SK
Dont be a blowhard Strenuous nose blowing can cause temporary or pennanent hearing loss by rupturing the delicate structures inside the eardrum To relieve nasal congestion adshyvises Nielsen gently blow one nostril at a time
Get screened If you have diabetes youre more likely to suffer earlier and faster hearing loss probably because of impeded blood flow to nerves that control hearing If you have diabetes in particshyular you really should consider getting a yearly hearing test just as you get annual tests for vision kidney function and other possible dishyabetes complications says Nancy Vaughan PhD a researcher at the National Center for Rehabilitative Auditory Research in Portshyland Oregon who has investigated the diabetes-early-hearing-Ioss link Those with high blood pressure or high cholesterol could also benefit from regular hearing screenings she adds
Watch your aspirin Aspirin is among the 200 or so medicashytions that can cause hearing loss by damaging hearing hair cells
and nerves that carry sounds to the brain This is not to say you should ditch your daily aspirin therapy But it does mean you should be diligent about following the typical recommended dosages for heart health and pain--and not take much higher doses YoulI know youre taking too much aspirin if your ears ring but the ringing stops when you stop taking aspirin
Smell and Taste When smell is impaired an inability to taste usually follows This not only makes eating less pleasurable it can also lead to other problems Smell and taste get the digestive process rolling by triggering saliva and gastric juices to help digest food says Marcia Levin Pelchat PhD a scientist at Monell Chemical Senses Center in Philadelphia the nations leading institute for smell and taste research Before food is even eaten these senses allow the body to anticipate food and make absorpshytion more efficient And when you cant smell or taste food youre less likely to eat it risking malnutrition Chew over the following strategies for preserving the flavor in your life
Breathe in If youre sitting down for a hot meal says Alan Hirsch MD director of the Smell and Taste Treatment and Research Foundation in Chicago take advantage of the cool fact that its good to snifffood before you eat because heat aermiddot ates odor molecules that youll perceive as taste
Hit the showers A less practical but equally effective varishyation on the above principle The heat and humidity of a warm shower clears sinuses and helps dissolve molecules that facilishytate the ability to smell says Hirsch Plus youll be nice and clean for dinner
Manage your sniffles People with recurrent colds or allergy problems are more vulnerable to smell and taste impainnent feshycause they often develop nasal polyps that block the sense recepshytors inside the top of the nose Hirsch adds Its most noticeable while they have a cold or allergies but frequent nasal or sinus problems can lead to chronic problems in the ability to smell
But rethink that cold remedy A zinc deficiency is one suspected cause of smell problems but that doesnt mean cold remedies containing this nutrient are a cure-all Zinc lozenges such as Cold-Eeze and zinc nose sprays that you can buy over the counter actually cause a temporary distortion in smelJ and taste especially in sweet sensations says Pelchat When you stop using them your nonnal senses of smell and taste usually return
Buckle up The single most common cause of a complete smell impairment Head injury like that sustained in a car accident says Hirsch Perhaps the easiest thing you can do to protect your senses of smell and taste is to always wear a seat belt while driving
Sid KJrchheimer last wrote for AARP The Magazine about scams (HRip-off Alert July-August 2004) He is also the author of a forthshycoming action guide that collects hundreds of tips on how to avoid conshysumer rip-offs (AARP BooksSterling spring 2006)
bull __tHdWtr~~
From AARP The Magazine SeptemberOctober 200S pp 24-27 Copyright 0 2005 by Sid Kirchheimer Reprinted by permission of the author
44
COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
ANNUAL EDIT10NS
Spark Your Sixth Sense
Just for fun we asked leading experts what can be done to maintain or enhance the sixth sense -abilities such as ESP telepathy and clairvoyance It turns out psychic abilities may actually benefit from aging Conditions that are more conducive for psychic experiences seem to ocshycur more readily in older people than in younger ones says researcher Emily Williams Kelly PhD of the Unishyversity of Virginias division of personality studies which studies psychic phenomena How better to get in touch with the other side Consider the following
bull Use the quiet When the house is absent of yelling kids blaring music and other immediate distractions youre more likely to be able to focus on the beyond These events seem to occur more readily in those who have them with quiet solitude and meditation says Kelly
bull Watch for signs People who are extroverted and open to the idea of having these experiences are more likely to show ESP abilities says Kelly And their glass is half fullft attitude includes taking clues from everyday events middotSigns are everywhere adds Lisa Nash a clairvoyant and online psychic reader at Global Psychic Inc Pay attention to what you see while you are driving It may be an indication of whats in your lifes path A dead deer on the side of the road might indicate that you are neglecting your inner power that comes from gentleness
bull Eat for illumination Nash says many psychics eat healthfully avoiding alcohol and drugs as well as
caffeine sugar and processed foods in order to maintain mental focus and clarity Meanwhile recent research shows that one of the omega-3 fatty acids found in heart-healthy fish such as salmon and mackerel can prevent age-related damage to a part of the brain where cells responsible for learning and memory communicate with one another -SK
Dont be a blowhard Strenuous nose blowing can cause temporary or pennanent hearing loss by rupturing the delicate structures inside the eardrum To relieve nasal congestion adshyvises Nielsen gently blow one nostril at a time
Get screened If you have diabetes youre more likely to suffer earlier and faster hearing loss probably because of impeded blood flow to nerves that control hearing If you have diabetes in particshyular you really should consider getting a yearly hearing test just as you get annual tests for vision kidney function and other possible dishyabetes complications says Nancy Vaughan PhD a researcher at the National Center for Rehabilitative Auditory Research in Portshyland Oregon who has investigated the diabetes-early-hearing-Ioss link Those with high blood pressure or high cholesterol could also benefit from regular hearing screenings she adds
Watch your aspirin Aspirin is among the 200 or so medicashytions that can cause hearing loss by damaging hearing hair cells
and nerves that carry sounds to the brain This is not to say you should ditch your daily aspirin therapy But it does mean you should be diligent about following the typical recommended dosages for heart health and pain--and not take much higher doses YoulI know youre taking too much aspirin if your ears ring but the ringing stops when you stop taking aspirin
Smell and Taste When smell is impaired an inability to taste usually follows This not only makes eating less pleasurable it can also lead to other problems Smell and taste get the digestive process rolling by triggering saliva and gastric juices to help digest food says Marcia Levin Pelchat PhD a scientist at Monell Chemical Senses Center in Philadelphia the nations leading institute for smell and taste research Before food is even eaten these senses allow the body to anticipate food and make absorpshytion more efficient And when you cant smell or taste food youre less likely to eat it risking malnutrition Chew over the following strategies for preserving the flavor in your life
Breathe in If youre sitting down for a hot meal says Alan Hirsch MD director of the Smell and Taste Treatment and Research Foundation in Chicago take advantage of the cool fact that its good to snifffood before you eat because heat aermiddot ates odor molecules that youll perceive as taste
Hit the showers A less practical but equally effective varishyation on the above principle The heat and humidity of a warm shower clears sinuses and helps dissolve molecules that facilishytate the ability to smell says Hirsch Plus youll be nice and clean for dinner
Manage your sniffles People with recurrent colds or allergy problems are more vulnerable to smell and taste impainnent feshycause they often develop nasal polyps that block the sense recepshytors inside the top of the nose Hirsch adds Its most noticeable while they have a cold or allergies but frequent nasal or sinus problems can lead to chronic problems in the ability to smell
But rethink that cold remedy A zinc deficiency is one suspected cause of smell problems but that doesnt mean cold remedies containing this nutrient are a cure-all Zinc lozenges such as Cold-Eeze and zinc nose sprays that you can buy over the counter actually cause a temporary distortion in smelJ and taste especially in sweet sensations says Pelchat When you stop using them your nonnal senses of smell and taste usually return
Buckle up The single most common cause of a complete smell impairment Head injury like that sustained in a car accident says Hirsch Perhaps the easiest thing you can do to protect your senses of smell and taste is to always wear a seat belt while driving
Sid KJrchheimer last wrote for AARP The Magazine about scams (HRip-off Alert July-August 2004) He is also the author of a forthshycoming action guide that collects hundreds of tips on how to avoid conshysumer rip-offs (AARP BooksSterling spring 2006)
bull __tHdWtr~~
From AARP The Magazine SeptemberOctober 200S pp 24-27 Copyright 0 2005 by Sid Kirchheimer Reprinted by permission of the author
44
COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
COMMON FLAVORS AROMAS AND CHEMICAL SIGNALS RELEASED FROM ANIMALS CAN MAKE THE MOUTH WATER EVOKE VIVID MEMORIES AND PERHAPS EVEN SIGNAL STRESS OR FERTILITY HOW DOES THE BRAIN SORT IT ALL OUT
SENSES BY RICHARD SALTUS ILLUSTRATION BY HANNAH STOUFFER
Dr Rosalyll M Killg Iltrodllctioll to PsycholOffl
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
Twenty-five years ago the physician
and writer Lewis Thomas predicted that
the progress ofbiological research would be
measured by how long it took to gain a
complete understanding of odor It may not
seem a profound enough problem to domishy
ilate all the life sciences he observed but it
contains piece by piece all the mysteries
How an organism recognizes a vast
universe ofodors is indeed a fascinating
problem in molecular recognition and
perceptual discrimination agrees Richard
xe an HHMI investigator at New Yorks
Columbia University
Put simply how do we know what were
smelling Scientists are exploring this quesshy
tion in everything from worms to fruit Aies
to mice to humans bringing a variety of
new molecular tools and computational
methods to bear
Only in the last decade and a half scienshy
tists including Axel and HHMI investigator
Linda Buck at Seattles Fred Hutchinson
Cancer Research Center have begun
breaking the code the olfactory system uses
to define different incoming odor moleshy
cules - the first step in recognizing them
They have revealed how the coded
information for a smell is represented or
~ ~
iJI gt11
mapped in certain parts of the brain
Now the scientists are in hot pursuit of the
next steps How does the brain transform
that map into meaningful neural informashy
tion so that odors will elicit appropriate
cognitive responses and behaviors ixel
says This is the central problem facing
my laboratory
The nasal cavity and the tongue are
laced with cells that detect chemical
compounds-millions of neurons in the
nose and specialized taste bud cells on the
tongue These cells are wired to relay
stations and processing centers in the
brain which are thought to create sensory
images of the perceived odors or Aavors
In parallel with the main olfactory
system used for odor sensing evolution has
also spawned a separate accessory olfacshy
tory system in some animals for detecting
pheromones -chemical signals used by
individuals of the same species to mark
territory warn of danger identify close
relations and induce mating
The lack ofaccessory olfactory structures
in humans has suggested a corresponding
lack ofhuman pheromones But interesting
new discoveries are rewriting the textbook
demonstrating that in some mammals at
least pheromones can be detected by the
odor-sensing olfactory system as well
READING Asmell begins when volatile
AN ODOR odor molecules (odorants)
dissolve in nasal mucus and bind with recepshy
tors in the olfactory epithelium - speCialized
tissue located in the upper-rear nasal cavity
(The convoluted olfactory epithelium in
humans if Aattened out would be the size
of a cookie while the equivalent area in a
bloodhound for example would be the size
of a small pizza) The odorant receptors are
located on olfactory sensory neurons which
transmit signals through their axons to the
olfactory bulb a relay station in the front of
the brain Olfactory bulb neurons in tum
transmit signals to the olfactory part of the
cortex which distributes olfactory infonnashy
tion to yet other brain areas
Mammals can detect at least 10000
different odors How the mammalian olfacshy
tory system can distinguish so many odorant
chemicals was a longstanding mystery until
1991 when Axel and Buck then his postshy
doctoral associate made a discovery that
opened a new chapter in olfactory research
They identified a gene family that encodes
about 1000 different types of olfactory
receptors in the mouse and a smaller
number about 350 in humans and then
independently went on to explore how
olfactory information is organized and
encoded in the nervous system In 2004
Axel and Buck were awarded the Nobel
Prize in Physiology or Medicine for their
discoveries of odorant receptors and the
organization of the olfactory system
They discovered that each neuron in
the nose expresses only one receptor gene
Thousands of neurons with the same
receptor are scattered in the nose but their
axons all converge in a few specific glomshy
eruli (spheroid structures) at two spots in
the olfactory bulb
18 HHMI BULLETIN I February 1007
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
Because of research by HHMI Investigators CHARLES ZUKER University of California San Diego LINDA BUCK Fred Hutchinson Cancer Center and colleagues
we know a lot more about taste-sensing cells than we did a decade ago
How does the olfactory system distinshy
guish among thousands ofodorants some
with nearly identical structures Bucks
group discovered that odorant receptors
are used combinatorially to encode odor
identities Just as letters of the alphabet
can be used in different combinations to
form a multitude ofdifferent words odorant
receptors are used in different combinashy
tions to create a vast array of different odor
perceptions says Buck In the olfactory
bulb each odorant is thus represented by
a unique combination or map ofglomshy
eruli at differing positions with a similar
activation profile in every individual
This map must be conveyed in some
form on to the next more complex levels
of processing in the brain Tracing these
pathways and events is for Axel something
most easily done in the simple nervous
system of the fruit fly With powerful
imaging techniques he can visualize indishy
vidual neurons connecting the flys
antennal lobe (analogous to the olfactory
bulb in mammals) to higher brain strucshy
tures In collaboration with HHMI
investigator David J Anderson and
Seymour 1 Benzer at the Caljfornia
Institute of Technology Axel has traced
the path of nerve signals that are activated
when the fly detects carbon dioxide gas a
component of a stress odorant that traushy
matized flies emit to warn other flies away
The researchers found that a single type of
olfactory neuron detects the COz and that
those neurons connect to a single glomershy
ulus in the antennal lobe By tracing this
simple dedicated circuit at successively
higher levels Axel hopes ultimately to
close the entire loop from input to output
In the mouse Buck and her colleagues
have traced the pathway from single types
of odorant receptors in the nose through
the olfactory bulb to the olfactory cortex
This work revealed that the cortex also has
a stereotyped map of odorant receptor
inputs However while inputs from
different receptors are segregated in the
olfactory bulb they are mapped onto the
cortex in a partially overlapping fashion
Moreover single cortical neurons appear
to receive signals from combinations of
odorant receptors suggesting that they
might integrate signals from different recepshy
tors that recognize the same odorant
Bucks group also reported that some
cortical neurons respond to a mix of two
odorants but not to either one alone We
think that what we are seeing in the cortex
may be an initial step in the reconstruction
of an odor image from its deconstructed
features which are encoded by combinashy
tions ofodorant receptor inputs Buck says
THE TASTE Flavors are made up of inputs IS IN THE
RECEPTOR from the taste buds of the tongue as well as from olfacshy
tory information stimulated by the aromas
of food wafting up into the rear of the
nasal cavity Taste-bud neuronal receptors
are sensitive to five basic qualities - bitter
sweet sour salty and umami (glutamate or
savory) These ancient senses likely
evolved for seeking nutrients and avoiding
toxins or spoiled food
The receptors were unknown untilI9l
when research groups headed by Charles S
Zuker an H HMI investigator at the
University of California San Diego and
Nicholas Ryba of the National Institutes of
Health isolated the first candidate taste
receptors now known as T I Rl and Tl R2
Then in 2000 Zuker Ryba and Buck
reported the isolation of the receptors for
bitter taste collectively known as the T2Rs
More than 30 different T2Rs exist reflecting
the importance of avoiding a wide range
of bitter substances many of which are
poisons Notably experiments by Zuker
Ryba and colleagues demollStrated that
the bitter taste receptors are a population of
bitter-sensing cells in the tongue that trigger
hardwired aversion signals
If so what explains the popularity of
coffee with its bitter caffeine taste as well
as beer and certain other bitter foods For
one thing says Zuker who likes darkly
February 2007 I HHMI BULLETIN 17
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
HHMI investigators RICHARD AXEL Columbia University and CATHERINE DULAC Harvard University are revealing the wiring of the systems involved in smell and pheromones respectively
roasted coffee and takes it black with sugar There is a reward associated with coffee and beer For another We like to live on the edge and have new sensory experishyences Ofcourse individuals vary in their taste for bitter substances causing some people to steer away from strong ales and to dose their coffee with cream and sugar
Not long after the bitter-receptor discovery Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes in the fall of 2006 the scientists reported that sour taste is detected by a completely separate populashytion oftaste cells expressing an ion channel protein called PKD2Ll The receptor for salt has still not been found
Zuker concludes that taste coding in the tongue and mouth is configured with elegant simplicity He writes It is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes And while certain areas of the tongue are more sensitive to some flavors than to others every area can respond to every flavor
A corollary that emerged from these studies is that taste is a property of the cells that are activated not of the food moleshycules-or even the receptors Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responshysive cells of mice and the animals reacted as if the compound tasted sweet Zuker and Ryba also generated mice that taste bitter
18 HHMI BULLETIN I February 1007
compounds as sweet Theres nothing bitter about bitter tastants and theres nothing sweet about sucralose [a sugar substitute] observes Ryba [t tastes sweet because when we put it on our tongue we get a particular pattern of neural firing
Ultimately Ryba and Zuker hope to trace taste signals from the tongue up into the brain where they are mingled with olfactory and other sensory information leading to cognitive and behavioral responses
FASCINATION WITH Communication via PHEROMONES pheromones occurs
in insects fish reptiles and mammalsshythough whether theyre significant in the lives of human beings is a fascinating and controversial question Pheromones have to do with making shortcuts in the brain to certain behaviors explains HHMI investishygator Catherine Dulac at Harvard University In a sense these pheromones are a byshyproduct of the animals internal state she says For example if an animal has a high level of testosterone the metabolites in its urine will be high and they act as a pheroshymonal signal ofdominance that goes out to both males and females in close proximity
It has long been thought that pheroshymonesmay be sensed exclusively by the accessory olfactory system In this system chemicals are detected in the vomeronasal
organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals Mostmammals and reptiles have a VNO whereas if a VNO exists in humans at all it is nonfunctioning
While working in Axels lab Dulac in 1995 was the first to identify a family of receptors in the VNO Two years later the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors In further studies Dulac identified additional components of the VNO signaling machinery
Given that the human nose lacks a funcshytional VNO is there any reason to think that people can communicate through pheromones Many scientists have been skeptical yet in the popular imagination a belief in some sort of sexual chemistry between human beings continues to thrive Vhether this is true remains unknown but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals-at least in some mammals possibly representing an evol utionary backup to the VNO for receiving these crucial communications
1112002 Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals Even without a working VNO they sensed fertility pheromones in the environment and went into mating mode But to the researchers surprise males could no longer distinguish between
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg
a male and female mouse-nor did they Ihw stereotypical aggression against other
males The experiment told us the VNO function is not required for mating behavior says Dulac What people were saying was the detector of the love potion - the VNO-was not true So there is something else in the olfactory system that is detecting cues and getting animals to mate
In another intriguing finding Buck and postdoctoral fellow Stephen Liberles reported in the August 10 2006 issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones These recepshytors called trace amine-associated receptors or TAARs were previously proposed to function in the brain as recepshytors for chemical messengers called trace amines However the researchers could not detect any of the 15 mouse TAARs in the brain whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose Each TMR gene is expressed by a unique set of neurons just like each odorant receptor gene
Zebrafish have 57 of these receptorsshymany or all found in the olfactory epithelium -and humans interestingly have six TAARs By testing TAARs with
more than 200 compounds Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine and one TMR recognizes a male pheromone that stimulates puberty in female mice The evolutionary conservashytion of TAARs their expression patterns in mouse and fish and the TAAR ligands we have identified so far together suggest that TAARs serve a different function ampom that of odorant receptors and that they may be involved in recognizing social cues such as pheromones Buck says Since humans have TAARs might they be capable of detecting pheromonal signals among people Thats a question Buck is pursuing
The discovery of TMRs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO Dulac and Buck have also found evidence in mice of connecshytions between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior So now if you ask the question Where are the neurons that detect pheromones Dulac says we can say that both the VNO and the main olfactory system are involved Why have animals developed two sensory systems to detect pheromones Dulac has shown
Industry scienshytists are using knowledge about the codes
for taste and smell to try to trick the sensory receptors and enhance the flavors of food create more healthful substitutes for sugar and salt or counter the bitter taste of medicines Most current applications involve taste receptors even though the olfacmiddot tory receptors were discovered first says Gary Beauchamp PhD president and director of the Monell Chemical Senses Center a nonprofit research institute in Philadelphia that once the receptors for smell were identified they could be put into cell systems in the laboratory then you could find out what compounds bind to the receptors
and this might be useful in designing odors of value But its been much more difficult to do than anyone would have guessed Beauchamp says
Monell scientists reported they had succeeded in maintaining rat taste receptor precursor cells in culture for up to two months and planned to try growing human taste cells in a similar manner rhis has the potential for practicality Beauchamp says
that the brain coding ofVNO information is very different ampom the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds
lfthese discoveries carry over to humans they could help explain intriguing observashytions of what appear to be pheromone-like communications between people-even in the absence of a functioning VNo Among them the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more chemistry with individuals whose imrnune systems are genetically different (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells)
THE LURE OF Clearly an enormous THE PURSUIT amount of work lies ahead
to reach Lewis Thomass goal of undershystanding smell-as well as taste and the mechanics of pheromone sensing Yet the lure of the pursuit remains strong among researchers the biotech and food indusshytries and curious people everywhere
Our sensory experiences represent a beautifully orchestrated response to a wide range of stimuli says Zuker The chemfcal senses capture the imagination of scientists and the public because we can so easily relate to them and because they have the potential to lead to products that can improve diet health and the way we live _
a California bioshytechnology company of which HHMI investigator Charles Zuker is a founder and Catherine Dulac is a scientific advisory board member is developing several products aimed at the food industry One a spinoff of the discovery of the umami receptor is aimed at creating a savory flavor-enhancing substitute for MSG (monosodium glutamate) and the company plans to sell it to China which has the worlds largest market for MSG
also at work on natural and synthetic compounds as high-potency sweeteners to
reduce the need for high-calorie carbohydrate sweeteners in foods and drinks and on compounds that can block bitter receptors in taste cells
bitter sensation and taste could make otherwise unpalatable food sources such as soy protein more desirable as well as medicines that leave a bitter aftertaste says Zuker Who knows-such a product might even lead to a cup of coffee with no bitterness even taken black -RS
February 1007 I HHMI BULLETIN 19
Sa1tus Richard Common Senses HHMI Bulletin 20 (February 2007) 14-19
copy 2007 Howard Hughes Medical Institute
HHMI HOWARD HUGHES MEDICAL INSTITUTE
4000 Jones Bridge Road Chevy Chase Maryland 20815-6789 wwwhhmiorg