Circadian Rhythms: Lecture 4

Proseminar in Biological Psychology

Circa: "about” Dies: “day"

Circadian rhythms are physiological and behavioral characteristics that follow a daily, or circadian, pattern

Circadian Rhythms

24 hour period

Biological Rhythms

Ultradian: cycles lasts shorter than a day- milliseconds it takes for a neuron to fire- 90 minutes sleep cycle (REM and NON REM sleep)- hunger- YOUR ATTENTION SPAN IN CLASS!

Infradian: cycles lasts longer than a day- monthly menstrual cycle- hibernation in animals- bird migration

Circadian: cycles lasting 24 hr- sleep-wake cycle- body temperature- testosterone levels: highest around 6:00 am, low

at 6:00 pm

What dictates or governs our 24 hr cycle?

Environmental Cues: the light/dark cycle

Zeitgerbers: German for “Time Giver”

-Meals-Temperature-Social activity-The tide (marine animals)

Entrainment

Zeitgebers

….no circadian rhythms?

We Do Not Need Environmental Cues for Circadian Rhythms

• Persistence of rhythm in constant conditions(LL/DD) & (Temp): tend to drift.. Under natural

conditions, the clocks are precise. • Rhythm can be entrained

So CR=daily rhythm is endogenously generated,

but still susceptible to modulation by 24-hour environmental cycles

endogenous "clock

How do we know that these rhythms aren't entirely environmentally induced?

French Astronomer

Jean Jacques d’Ortous de Mairan (1729)

Heliotrope leaves closed at night

Observed the persistence of leaf movement in plants placed in

constant dark

For 2 centuries nobody cared!!!

First Time Evidence for a Endogenous Clock

Psychiatrist August Forel

(1910)Noticed bees returning to

the breakfast table at the

same time of day to get jam

Psychiatrist August Forel

(1910) the bees returned at the same time of the day even when the food was not present

Hey Fred, where’s the jam?

von Frisch & Beling (1920) First experiment done in the lab setting

1. Used Bees – set out sugar in water for several days

2. Bees came as expected

3. When not offered bees continued to show up

4. Performed the experiment in a salt mine = same result

1931 – Wiley Post (Aviator)Flew eastward around the

world in 8 1/2 days (208 hrs)

- flying ability adversely affected

- sleep was disrupted- general feeling of

uneasiness- nausea

First person to report JET LAG internal clock not adjusted to

environmental clock

Early Human Evidence of an Endogenous Clock

•Blind animals still show circadian rhythms

Other Evidence

- Some strains of Mice have virtually no retinabut still have circadian rhythms

- Blind people show circadian cycles

Put Animals & Humans in “Constant Conditions”

Constant Conditions: LIGHT/LIGHT DARK/DARK

“Free Running” = without cues

How close is the endogenous clock to 24 hr cycle?

Depends on the Species

Mus musculus (mouse) = 23.5Homo Sapiens (Humans) = 25?24.18Mesocricetus auratus (Hamster) = 24.1

The ‘natural’ period of a biological rhythm free-running in constant conditions:

TAU

Running Wheel ActivityMeasurement of Tau

Onset of running wheel activity is used

the phase indicator while free Running = CT12

14L/10D

Mouse (23.5) Hamster (24.1)

Actogram

Measurement of Tau in humans

Actiwatch

The Clock – Oscillator

Suprachiasmatic Nucleus

SCN

Densely packed collection of small cells(only 20,000) anterior hypothalamus

Midline in a shallow impression of the optic chiasm

                                            

           

SCN - Biological ClockSCN - Biological Clock

Suprachiasmatic Nucleus (SCN)

Feeding, sleep, temperature, hormones

SCN neurons project to other hypothalamic regions

Sleep & waking (Ventral)Sub paraventricular Zone

Body Temp (Dorsal)Sub paraventricular Zone

Retina-Geniculate-Striate Pathway – Ventral View

Anterior Portion of the Hypothalamus (SCN)

Superior to optic chiasm, receives input from optic nerves (RHT); this input synchronizes the “clock” in the SCN to the exterior day-night cycle

Retino-hypothalamic Tract

SCN

Innervation of the Pineal Gland in

Humans –needs SCN

Dependent on the

Light/Dark Cycle

Evidence for SCN - Biological Clock

1900’s Simpson & Galbriath

Rectal Temp every 2 hours for 2 months!!!!!

• Lesions here interfere with circadian rhythms

1967 – C. P. Richter (rats)Hypothalamic Lesions = disrupted eating, drinking, activity

1972

Evidence for SCN - Biological Clock

Moore & Eichler Stephan & Zucker

SCN

Lesions disrupted running wheel activity, drinking, hormones

•Lesions here interfere with circadian rhythms (rodents, primates)

-Still show rhythms but desynchronized to environment L/D cycles (sleep at inappropriate times)

-Abolishes rhythms completelyfeeding, locomotor activity, sleep, temperature, hormones

Evidence for SCN - Biological Clock

Important! Changed the pattern of sleep not the

amount

                                            

           

SCN - Biological ClockSCN - Biological Clock

SCN

day night

Increased metabolic activity (Schwartz & Gainer, 1977)

So..SCN keeps track of day or nightBut not whether you are diurnal or nocturnal

Injected 2-DG in rats…same results in squirrel monkeys

•SCN cells invivo and invitro confer rhythminicity - in tissue culture - transplantation

Electrophysiological studies - electrical activity continues even

after surgical removal from hypothalamus- other brain sites also show this but

need a connection the SCN

•Lesions of visual cortex have no effect on rhythms

•Severing RHT = free running rhythm

Other Major Evidence for SCN - Biological Clock

SCN neurons (4)All show circadian rhythms

Displaying individual rhythms

…coolio

Tissue Culture

Electrophysiological studies - electrical activity continues even after surgical removal from hypothalamus

Remove clock from the animal and clock still exhibits a sustained circadian rhythm

Transplantation Studies – Cooler Stuff

Ralph et al (1990)

Removed SCN from Mutant Hamsters (short tau 22 hrs)

Transplanted SCN into hamsters that had lesioned SCN

Restored….Sleep/Wake Cycle….not regular cycle BUT….the short rhythms!!

VISA VERSA…same results!!!! transplant to Mutants

Ralph, M. R. and Menaker, M. (1989)

Transplantation Studies – Coolest Stuff

Silver et al (1996)

Lesioned SCN of Hamster = abolished rhythms

Got donor SCN placed in tiny semipermeable capsuletransplanted into III ventricle

Chemicals, nutrients in NO SYNAPTIC TRANSMISSION

Reestablished rhythms!??? Chemical

What makes the clock tick? Hands of the SCN

“Main Oscillator” (SCN cells)But what about at the molecular level?

GENES (contain the instructions that tells a cell

what its job will be)

Cells contain a newly discovered protein (clock protein)

that regulates gene function and which shows 24-hr

variations in cellular levels that appears to account for

24-hr variations in neuronal activity