1.History of Neuroscience and Org. of the Brain

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    THEUNI

    VERSIT

    YOF

    CALIFORNIA

    BERKELEY

    1868

    LETTHEREBE

    LIGHT

    Molecular & Cell Biology

    Mammalian Neuroanatomy Fall, 2012

    David Larue

    MCB 163

    Henk Roelink

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    PersonnelInstructors:

    DavidLarue,LecturerinNeurobiologyOfficehours:Friday;2:004:00pmorbyappointment398LSA

    HenkRoelink,Assoc.ProfessorofGenecs,GenomicsandDevelopment Officehours:Friday; 1:00 3:00 pm or by appointment

    21KoshlandHall GSIs:

    Timothy Day Flannery and Schaffer labs (HWNI) Tuesdaylabs(secons1and2)

    Officehours4:30-5:30pmTuesday(aWerlab) room4048VLSB

    Caleb Smith Kramer Lab (MCB-Neuro) Thursdaylabs(secons3and4)

    Officehours4:30-5:30pmThursday(aWerlab) room4048VLSB

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    Academicbackgroundandinterests

    DavidLarueundergraduate:UCSantaCruz:BiologyandPsychology,1975 graduate:UCSanFrancisco:Anatomy,1981

    researchinterest:anatomyandneurochemistryofthe

    centralauditorypathways

    HenkRoelinkgraduate:UniversityofAmsterdamandStanfordUniversityresearchinterest:molecularnatureofsignalingmoleculesguidingtheinduconofdisnctneuronpopulaonsinthedevelopingCNS

    TimothyDayundergraduate:UniversityofKansas

    researchinterest:improvedviralvectorsfortransgenictherapies

    forrenaldegeneraon

    CalebSmithundergraduate:GrinnellCollege

    researchinterest:useoflightmodulatedGABAreceptorsinthe

    studyofdendricintegraonandsynapcplascity

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    Lecture 1:

    History of Neuroscience and the

    Organization of the Nervous System

    Neuroanatomy takes brains!

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    TheOriginsofNeuroscience

    Prehistoricancestorsclearlyunderstoodthatthebrainwasvitaltolife Skullsurgeries

    Evidence:Trepanaoninbotholdandnewworldcultures,EgypanandIncamummies.

    Skullsshowsignsofhealing

    AncientGreece Correlaonbetweenstructureandfuncon Hippocrates

    Brain:Involvedinsensaon;seatofintelligence

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    TheRomanEmpireClaudiusGalen,aGreek,wholivedinthe2ndcentury

    intheRomaneraisconsideredtobethefatherofmodernmedicine.ThegreatveinofGaleninthe

    brainbearshisname.Hepioneeredhygieneandinsisted

    onwelllitandvenlatedroomsforhealing.Galeneven

    performedcataractsurgeriesafeatnotmatchedfor

    nearlytwomillennia!

    Galenthoughtthebrains

    ventriclespumpedfluid

    throughthenervestoeffect

    musclemovementlikea

    hydraulicsystemcalledthe

    Fluid-Mechanicaltheoryof

    brainfuncon,anoonthat

    enduredforalmost1500years

    TheOriginsofNeuroscience

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    DaVinci[14521519]Hisaccomplishmentscannotbeoverstatedandanatomywasoneofhispassions.Herehe

    depictshisinterpretaonofGalensviewoftheventricles

    centralroleinmovementandevenvision.

    AndreasVesalius[15141564]wasananatomist,physician,andauthorofoneofthemostinfluenalbooksonhuman

    anatomy,Dehumanicorporisfabrica(Ontheorkingsofthe

    HumanBody).VesaliusisoWenreferredtoasthefounderof

    modernhumananatomy.BornAndreasvanesel,likeallacademicsoftheday,heLa

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    TheRenaissance:Thebrainasamachine

    TheFrenchmathemacian/philosopher,ReneDescartes[1596-1650]wasaproponentofGalensFluid-Mechanical

    theoryThehollowventriclesofthe

    brainseemedtoharmonizewiththose

    oftheheart. Hethoughtthiswouldonlyexplainthe

    moremechanicalbehaviorofanimals

    Hedrewaclearlinebetweenhumanandanimalthathasinfluencednatural

    philosophyeversince Hebelievedthepinealglandwasthe

    seatofthesoul(seeaboveright),his

    schemeofvisioninvolvedthe

    projeconofimageswithinthe

    ventriclesontothepinealgland

    TheOriginsofNeuroscience

    The Eighteenth CenturyGray matter and white matter distinctions

    observed. Gyri, sulci, and fissures andmodern observations of brain injury led to

    hypotheses of function

    1791 Luigi Galvani [1737-1798]

    discovered muscular twitch associatedwith electrical current: "On the Effect of

    Electricity on Muscular Motion

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    TheOriginsofNeuroscience TheNineteenthCentury:Modernity

    1808FranzGallphrenology

    1811-CharlesBelltracedthecourseofspinal

    nervesanddisnguisheddorsalfromventralroots

    1817-JamesParkinsonpublishedthefirst

    descriponofshakingsyndromethatnowbearshis

    name

    1821-FrancoisMagendierepeatsBellsstudyand

    showssensoryandmotorfunconofdorsaland

    ventralroots(knownastheBell-Magendielaw)

    1821-Belldescribesfacialparalysis(Bellspalsy)

    1825LuigiRolandodescribedthecentralsulcus

    andsubstanagelanosaofthespinalcordboth

    ofwhichbearhiseponym

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    TheOriginsofNeuroscienceTheNineteenthCentury(cont.)

    1837-JanPurkyne(Purkinje)describes

    largeoutputcellsofthecerebellum

    1838-TheodorSchwanndescribesmyelin

    creaonintheperipheralnerves,

    proposedhiscelltheorytwoyearslater

    1848-PhineasGagesheadisimpaledby

    atampingrodinarailroadconstrucon

    accidentlobotomy

    1849HermannvonHelmholtzmeasures

    speedofimpulsesinfrogsciacnerve

    1859-RudolphVirchowcoinstheterm

    neuroglia1861-PaulBrocaspeechmotor

    funcon

    1872-GeorgeHunngtondescribesa

    hereditarymotorafflicon

    1873-CamilloGolgipublisheshissilver

    nitratestainforneurons

    1884-FranzNissldescribesthegranular

    endoplasmicreculum("Nisslbodies")

    1884-GeorgesGillesdelaTouree

    describesseveralmovementdisorders

    1885-Carleigertintroducesmyelin

    stainusinghemotoxylin

    1889RamonyCajalpresentsneuron

    doctrine

    1889-CarloMarnodescribescorcal

    neuronwithascendingaxon

    1897-CharlesSherringtoncoinsterm:

    "synapse

    1898BayerDrugCo.marketsheroinas

    non-addicvemorphinesubstute

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    TheOriginsofNeurosciencePhrenology

    Phrenology is the study of the structure of the skull todetermine a person's character and mental capacity.

    The Viennese physician Franz-Joseph Gall,(1758-1828) claimed there are some 26 "organs" on

    the surface of the brain which affect the contour of the

    skull, including a "murder organ present in killers.

    In1809Gallbeganwringhisgreatestwork:"TheAnatomyandPhysiologyoftheNervousSysteminGeneral,andoftheBraininPar

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    Phrenologicalmaps

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    Brocaandthelocalizaonoffuncon

    LocalizaonofFunconintheBrain

    PaulBroca,18241880,FrenchPhysicianandanatomist.

    Studyingaphasias,(theinabilitytospeakcoherently),he

    discoveredadiscreteregionofthehumancerebrumfor

    speech.HismostfamouspaentwasnamedLeborgne,

    nicknamed"Tan"duetohisinabilitytoclearlyspeakany

    wordsotherthan"tan.Postmortemstudyshowedalesionfromterarysyphilisintheventroposteriorfrontal

    lobe.ThisareahasbecomeknownasBrocasarea.

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    NeuroscienceToday

    Systems:sensoryormotor,anatomyandphysiology Cellular:anatomyandphysiologyofneuronsandgliasynapc

    formaonplascityandstudyofneuralcircuitry

    Neurochemistry:thediversityofneurotransmiersandreceptorsformthefoundaonformodernneuropharmacology

    Behavioral:psychology,ethology Comparaveneuroanatomy:focusontherelaonshipbetween

    behavioralspecializaon,anatomicalstructureandevoluonof

    phenotype

    Cognive:integrave,muldisciplinarystudyofhigherfuncons(fMRI,etc.)usinghumansubjects

    Computaonal:studyofbrainfunconintermsoftheinformaonprocessingproperesofthenervoussystem

    Moleculardevelopment:neurogenomics,homeoboxgenes,DNAmicroarrays

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    BasicDivisionsoftheNervousSystem

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    TypesofSensoryandMotorInformaon

    Copyright2008PearsonEducaon,Inc.,publishingasBenjaminCummings

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    Orientaonvectors

    Most vertebrates are quadripedswith their neuraxis roughly

    parallel to the ground.

    Bipedal primates (like us) walkwith the spinal neuraxis

    perpendicular to the ground.

    This can lead to some confusion

    in the orientation vectorterminology.

    Rostral means toward the beak

    Caudal means toward the tail

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    Orientaonvectors

    Thus,inarat,thetermsrostral,caudal,dorsal

    andventralare

    consistentthroughthe

    enreneuraxis.

    Inhumans,dorsalandventralinthebrainbecomerostraland

    caudalinthespinalcord.

    inotherwords,wegenerallytreatthehumanbrainandspinal

    cordseparatelywith

    respecttodireconal

    vectors

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    Orientaonanddireconaltermsinanatomy

    O i t d Di

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    OrientaonandDireconsynonyms

    Rattus norvegicus

    l f f h b

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    Planesofreferenceinthebrain

    Horizontal Coronal ortransverse Sagittal/mid-sagittal

    Because of the cephalic flexure in primates, the spinal axis is roughly

    perpendicular to the cerebral axis. Thus, a plane that is horizontalin the brain,

    is transverse or coronalin the spinal cord and the trunk. A transverse plane

    through the brain, becomes a longitudinal coronalsection through the body

    and spinal cord, while sagittalplanes are the same at every level.

    Are you confused yet?

    Th S i l C d (CNS) d S i l N (PNS)

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    TheSpinalCord(CNS)andSpinalNerves(PNS)

    Cervical enlargement

    Lumbar enlargement

    O i f S i l G d hi M

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    Gray Matter - dominated by neuronal cell bodies and neuroglia cells H or butterfly shaped

    Horns - anterior (ventral), lateral, posterior (dorsal) (sensory &

    motor nuclei)

    Gray commissure - axons crossing from one side to other Central canal - (continuous with the ventricles of the brain).

    White Matter - large numbers of myelinated and unmyelinated axons

    Arranged in columns of ascending and descending axons.

    contain tracts: sensory or motor; axons in same direction

    OrganizaonofSpinalGrayandhiteMaer

    D l t l h

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    Dorsal-ventralhorns

    D l t l h

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    Dorsal

    Ventral

    Graymaer

    hitemaer

    CentralcanalTracts(columnar)

    nuclei

    horns

    Dorsal-ventralhorns

    Dorsalroot

    ganglion

    B i hi hl i li d

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    Brainsarehighlyspecializedto scale

    the form of a mammals brainderives from many factors:

    body size determines the

    overall size and complexity ofcortical folding

    relative size of certain regions

    of brain reflect behavioraldependence on a particular

    sensory modality or motorbehavior hypertrophy of the

    auditory midbrain in echolocatingbats is one example

    note the enormous cerebellumof the dolphin their brain size is

    impressive but so it their overallmass: 330-1435 lbs!

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    MajorSubdivisionsoftheBrain

    Telencephalon-Cerebrum,Basalganglia

    Diencephalon-Thalamus,hypothalamus

    Mesencephalon-Midbrain-tectum

    Metencephalon-Pons,cerebellum

    Myeloencephalon-Medullaoblongata

    thalamus means room, or chamber

    tectum means roof

    pons means bridge

    medulla means core

    l f h b

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    Lateralaspectofthebrain

    l d l l l

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    Bloodsupply-lateralaspect

    middle cerebral artery isthe largest branch of the

    internal carotid and the

    site of most strokes

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    Dorsalandventralaspectsofthebrain

    central sulcus

    pons

    Bl d l t l t

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    Bloodsupply-ventralaspect

    The circle of Willis, a crucialarterial anastomosis (joining of twoindependent blood supplies) between the

    internal carotid and the basilar/vertebralarteries, is a clinical hotspot in neurology.

    As many as 80% of arterial aneurysmsoccur here. It is often diagnosed becauseof visual disturbances resulting from

    pressure on the optic chiasm/nerves.

    Tumors or cysts on the pituitary gland cancreate similar visual signs that lead to anearly diagnosis.

    M di l

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    Medialaspect

    corpus callosum

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    Bloodsupply-medialaspect

    Venous drainage

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    Venousdrainage

    (of Galen)

    Brain Stem common core of vertebrate brains

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    Copyright2003PearsonEducaon,Inc.publishingasBenjaminCummings

    BrainStem:commoncoreofvertebratebrains

    Some include the diencephalon

    B i t d l i

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    Brainstemdorsalview

    Diencephalon

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    Figure 7.15

    Epithalamus*

    Hypothalamus

    Thalamus

    Diencephalon

    Homeostatic regulation

    Sensory relay -target of descending

    cortical feedback* epithalamus includes thepineal gland, stria medullaris

    and the habenula

    Surface features of the human cortex

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    Surfacefeaturesofthehumancortex

    Corcal areas I

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    CorcalareasI

    Sensory and motor processing and higher cognitive functions

    Corcal areas II

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    CorcalareasII

    Somatosensory and motor maps - (the homunculus)

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    Somatosensoryandmotormaps (thehomunculus)

    Deep cerebrum: the basal ganglia (nuclei)

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    Deepcerebrum:thebasalganglia(nuclei)Pre-motor planning and coordination: inhibition of unintentional movements

    Basal ganglia (nuclei) in horizontal secon

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    Basalganglia(nuclei)inhorizontalsecon

    Basal ganglia are involved in several movementdisorders, including Parkinsons disease, Huntingtons

    Chorea, tic disorders like Tourettes Syndrome andeven obsessive-compulsive disorder (OCD)

    M t l i i t i t ti iti hi h f tiCerebellum

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    Motor learning, sensorimotor integration, cognitive higher functionsCerebellum

    The cranial meninges

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    3 connective tissue layers (one menix two or more meninges)

    Continuous with the spinal meninges

    FUNCTIONS:

    1. Cover & protect the CNS2. Protect blood vessels and form sinuses3. Contain CSF4. Form partitions within the skull

    Thecranialmeninges

    Meningeal layers

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    1. DURA MATER (tough or hard mother)

    Forms flat partitions provides stabilization and support for the brain and

    limits excessive movement

    Falx cerebri attaches to the crista galli (cocks comb) of the ethmoid bonein the anterior cranial vault.

    Tentorium cerebelli separates the cerebrum from the cerebellum

    Subdural space

    2. ARACHNOID (spiderweb-like)

    Unlike the dura and pia mater, the arachnoid is not always observed as a

    discrete membrane but rather as the inner lining of the dura. It does not

    extend down into the sulci. The space beneath it is filled with CSF and

    criss-crossed with a lacy matrix of fine fibers that led to its name.

    Subarachnoid space

    3. PIA MATER (soft mother)

    Delicate, highly vascular membrane clings tightly to brain over every sulcus

    and gyrus

    Meningeallayers

    Meningeal architecture

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    Meningealarchitecture

    Cerebrospinal Fluid & the Ventricles

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    CerebrospinalFluid&theVentricles

    the choroid plexus creates CSF in the ventricles the arachnoid villi reabsorb it

    Cerebrospinal Fluid & the Ventricles

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    CerebrospinalFluid&theVentricles

    Choroid plexus

    (one in each ventricle)

    arachnoid villus (granulation)

    capillaries ependymal cells

    Ventricles of the brain

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    Contain CSF, a cell-free ultrafiltrate of blood formed by the

    CHOROID PLEXUSES there are 4 one in each ventricle

    Continuous with each other

    1st and 2nd are the lateralventricles in the cerebral

    hemispheres

    3rd in diencephalon

    4th between pons& medulla oblongata(continuous with thecentral canal of thespinal cord)

    Ventriclesofthebrain

    Circulaon of cerebrospinal fluid (CSF)

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    CSFAbsorponofCSF

    returns

    tovenousblood

    Circulaonofcerebrospinalfluid(CSF)

    CIRCULATION OF CSF

    Replaced every 8 hours

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    enoughfordayone