A.1Neuraldevelopment

Fillerwords

1.Outlinehowtheneuraltubeofembryonicchordatesisformedbyinfoldingof

ectodermfollowedbyelongationofthetube

Thedevelopmentofthehumancentralnervoussystembeginsintheembryoduringthefirst

12weeksafterconception.Asimilarpatternofdevelopmentcanbeobservedinall

chordates(vertebratesandotheranimalsthatpossessasupportingdorsalrodcalleda

notochord).Intheembryonicectoderm,anareaofcellscalledtheneuralplatedevelops

andbecomesaregionknownastheneuralgroove.

Itisthesecellsthateventuallybecomethebrainandspinalcord.Thecellsoftheneural

plategraduallychangeanddevelopintofolds,whichextendupfromitandeventuallymeet

andcloseovertobegintheformationofatube.Inthisway,asthegrowthofthefolds

continues,theneuralgroovedevelopsintotheneuraltube.Thetubeelongatesanditsouter

cellsformthefoundationofthenervoussystem-cellsattheanterior(front)endbecomethe

brainandthoseintheposterior(back)regionbecomethespinalcord.

neuralplate

ectoderm--------

neuraIfold--------———n]

Wneuiral'growove

groove尸7一

deepens心

i

neuralgroove

closesovertox__neural

formneuralL~JX—-4crestcells

neural,tubbeZ\

separatesfrom

ectoderm

2.Explainhowneuronsareinitiallyproducedbydifferentiationintheneuraltube

Therearebillionsofneuronsinthecentralnervoussystem(CNS),mostoftheminthebrain.

Theoriginsoftheseneuronscanbetracedbacktotheearlystagesofembryonic

developmentwhenpartoftheectodermdevelopsintoneuroectodermalcellsintheneural

plate.Althoughnotyetneurons,thedevelopmentalfateofthesecellsisnowdeterminedand

itisfromthemthatthenervoussystemisformed.

Theneuralplatedevelopsintotheneuraltube,withthecontinuedproliferationofcellsby

mitosisanddifferentiationalongthepathwaysleadingtothecellsbecomingfunctioning

neurons.ThematureCNShasfarmoreneuronsthanwhatisinitiallypresentinthe

embryonicneuraltube,socellproliferationcontinuesinboththedevelopingspinalcordand

brain.Althoughcelldivisionceasesbeforebirthinmostpartsofthenervoussystem,there

aremanypartsofthebrainwherenewneuronsareproducedduringadulthood.

3.Describehowimmatureneuronsmigratetoafinallocation

Neuron

(signalling)

StemcellGlialcell

(selfrenewing){support)

Withinthedevelopingbrain,neuronsmigratetodifferentareasandbegintoconnectwith

otherneuronstomakeupneuralnetworks.Astheembryoandthenthefetusdevelops,

neuronsthatareproducedinthedevelopingbrainmigratetodifferentpositions.Somemove

byamethodknownassomalmigrationinwhichaneuronmovesbyextendingalong

processfromitscellbodytotheouterregionofthebrain.Thisregionwilllaterbecomethe

cortex.Thelongprocessattachesitselftotheoutersurfaceofthebrainandthecellnucleus

thentravels,throughitscytoplasmtotakeupanewposition.Onceyoungneuronshave

reachedtheirtargetregion,theymustbecomepartofanetworkinordertobeableto

processinformation.

Neuronsneedtodeveloptheaxonsanddendrites(extensionsoftheircellbodies)that

enablethemtocommunicatewithotherneurons.Axonssendsignalsawayfromtheneuron

cellbody,whiledendritesreceivesignalsfromotherneurons.Eachcelldevelopsanetwork

ofmanydendritesclosetothecellbodyandasingleaxonthatcanextendforsomedistance

awayfromthecell.Everyaxonextendsfromanareaknownasa'growthcone'atthe

extremeendoftheaxon.

Thegrowthconerespondstoandisguidedbymoleculesofcertainchemicalsubstances,

whichdirectittothecorrectarea.Someofthesechemicalstimuliareattractivewhileothers

repelthegrowingaxon.Axonsdevelopwithintheareasthatwillbecomethebrainbutalso

extendbeyondtheneuraltubetoreachotherpartsofthebody.Whenanaxonhasreached

itstargetarea,itbeginstodevelopmanysynapseswithothercells.Everydeveloping

neuronformmultiplesynapsesandthesesynapsesallowforcommunicationbetweenthe

cellsofthenervoussystemvianeurotransmitters.

4.Outlinehowanaxongrowsfromeachimmatureneuroninresponseto

chemicalstimuli

Animmatureneuronconsistsofacellbodywithcytoplasmandanucleus.Anaxonisalong

narrowoutgrowthfromthecellbodythatcarriessignalstootherneurons.Onlyoneaxon

developsoneachneuron,butitmaybehighlybranched.

Manysmallerdendritesthatbringimpulsesfromotherneuronstothecellbodymayalso

develop.Chemicalstimulidetermineneurondifferentiationwhentheaxongrowsoutfrom

thecellbodyandalsothedirectioninwhichitgrowsinthedevelopingembryo.

Axonsgrowattheirtips.Insomecases,theyarerelativelyshortandmakeconnections

betweenneuronswithinthecentralnervoussystem,butotherneuronsdevelopverylong

axonswhichcanreachanypartofthebody.Despiteonlybeingoutgrowthsofasinglecell,

axonscanbemorethanametrelonginhumansandmanymetreslonginlargermammals

suchasbluewhales.

AxonGuidancebvChemicalSignals

Axonscarryimpulsestootherneuronsortocellsthatactaseffectors-eithermuscleor

glandcells.Aslongasthecellbodyofitsneuronremainsintact,itsaxonmaybeableto

regrowifseveredordamagedinotherwaysoutsidethecentralnervoussystem.

Regrowthratescanbeasrapidasvemillimetresperdaysosensationorcontrolofmuscles

cansometimesreturnovertimeafterdamage.Ofcourse,thisrecoverydependsonthe

correctconnectionsbeingre-establishedbetweenanaxonandthecellswithwhichitshould

becommunicating.

5.Statethatdevelopingneuronformsmultiplesynapses.

Thegrowthofanaxonordendriteisdirectedsothatitreachesacellwithwhichitinteracts.

Asynapseisthendevelopedbetweentheneuronandtheothercell.Theaxonsofmotor

neuronsdevelopsynapseswithstriatedmusclefibresorglandcellsforexample.Synapse

developmentinvolvesspecialstructuresbeingassembledinthemembranesoneitherside

ofthesynapseandinthesynapticcleftbetweenthem.

Thesmallestnumberofsynapsesthataneuroncouldtheoreticallyhaveistwo-oneto

bringimpulsesfromanothercellandanothertopassthemon.Inpractice,mostneurons

developmultiplesynapsesandsomeneuronsinthebraindevelophundreds,allowing

complexpatternsofcommunication.

TypesofSynapseswithintheCentralNervousSystem

Manysynapsesareformedatanearlystageofdevelopment,butnewsynapsescanbe

formedatanystageoflife.Synapsesoftendisappeariftheyarenotused.When

transmissionoccursatasynapse,chemicalmakersareleftthatcausethesynapsetobe

strengthened.Synapsesthatareinactivedonothavethesemarkerssobecomeweakerand

areeventuallyeliminated.Themaxim"useitorloseit"thereforedescribessynapsesvery

well.

6.Explaintheprocessofneuralpruning

Duringhumandevelopment,thereisanenormousamountofcellgrowth,butthedeathof

neuronsisalsoimportant.Naturaldeathofcells(apoptosis)removesabouthalfofthe

neuronsincertainregionsofthebrainand,inaddition,thesecondtypeofcellmodification

knownas'neuralpruning'removesuptohalfthesynapsesthathavedevelopedbetween

neurons.

6years

SynapticPruning

Thesetwotypesofcelldeathareessentialtoremoveunusedneuronsandtherebyhelpto

establishandstreamlinethecomplexnervenetworksinthebrain.Thetimingofthetwo

typesofcelldeathisdifferent:mostcelldeath(apoptosis)occursbeforeababyisbornbut

mostneuralpruningandsynapticmodificationoccurafterbirth.

7.Explainhowtheplasticityofthenervoussystemallowsittochangewith

experience

Brainplasticityistheabilityofthenervoussystemtochangeinbothstructureandfunction

overaperson'slife,astheyreacttothechangesintheirenvironment.Asapersonacquires

newknowledge,learnsnewskills,orhasnewexperiences,thebraincanestablishnew

neuralpathways.Throughpracticeandrevision,communicationbetweensynapsesis

enhancedandsignalstravelmoreefficiently.

Later,ifthesameneuralpathwayisusedagain,theconnectionsbetweentheneuronsare

re-establishedandeachnewattemptmeansthatmemoryandcognitionaremadefaster.

Thissynapticplasticityisestablishedinasimilarwaytothewayawalkermightlearna

pathwaythroughafieldofcorn.Ifthepathisusedeveryday,aclearpathwillsoonbecome

establishedandthewalkerwillbeabletocrossthefieldmorequicklyandefficiently.

Mostofyouguysreadingthiscanexperiencesynapticplasticityasyoureviseforyour

exams.Ontheotherhand,ifsynapticconnectionsarenotused,pathwaysmaybelostand

unusedneuronscanberemovedduringneuralpruning.

MechanismsofNeuroplasticitv

Rerouting:NewconnectionsaremadebetweenSprouting:Newaxonanddendriteextensions

activeneuronstocreatealternateneuralpathwaysallowexistingneuronstoformnewconnections

NeuralconnectionsbyCollateralsproutingof

neuronAandneuronBneuronBafterdamage

PrimarypathSecondarypathTerminatedpathpriortodegenerationtoaxonofneuronA

Synapticplasticityenhancesconnectionsbetweenneurons,butasecondexampleofthe

changesthatcanoccurinthenervoussystemisneurogenesis,thebirthandproliferationof

newneuronsinthebrain.Formanyyearsitwasbelievedthatwhenneuronsdied,theywere

neverreplaced,butstemcellshavebeenfoundincertainareasofthebrain(the

hippocampusandthedentategyrus)thatareabletoreproduceandmigratetootherareas

ofthebrainwheretheyareneeded.Thismayoccurafteratraumaticeventsuchastroke,

whichk川smanybraincells.Neurogenesisallowsthebraintoreplacecellsthathavedied

andrestorefunctionsthathavebeenlost.Alternatively,insomecases,undamagednerves

indifferentareasofthebrainareabletotakeovertherolesofcellsthathavediedand

restoresomeofthefunctionslostwhenapersonhasastroke.

TedTalkaboutneuroplasicity

8.Determinethecausesofspinabifida

Spinabifidaisacongenitaldisordercausedwhentheneuraltubefailstocloseproperly

duringembryonicdevelopment.Somevertebraedonotformcompletelyandremainunfused

andopen,sothataportionofthespinalcordmaypassthroughtheopeninginthebones.

Thisoccursmostofteninthelowerbackinthelumbarorsacralvertebrae.Spinabifidacan

betreatedbysurgerysoonafterababyisborn.

Thesurgeonplacesthespinalcordbackintothebodyandclosesthegapbetweenthe

vertebrae,buttheaffectedpartofthespinalcordw川notbeabletofunctionnormally.Spina

bifidaisoneofthemostcommonbirthdefectsandoccursinapproximately1in1000births

worldwide.Folicacid,takenasadietarysupplementduringthefirstthreemonthsof

pregnancy,hasbeenfoundtogreatlyreducetheriskofspinabifidaandotherneuraltube

defects.

TypesofSoinaBifida

cerebrospinal

fluid

vertebral

meninges

body

SpinabifidaoccultaMeningocele

9.Outlinethepromotionofthereorganizationofbrainfunction.

ComparisonofVertebrae

NOFUSION

(foramenexposed)

-0、

Transverse

Body

process

(centrum)

NormalHumanVertebrae(Thoracic)SpinaBifidaVertebrae(Thoracic)

Anischemicstrokeisadisruptionofthesupplyofbloodtoapartofthebrain.Moststrokes

arecausedbyabloodclotblockingoneofthesmallvesselsinthebrain,butbleedingfroma

bloodvesselisanothercause.Duringastrokepartofthebrainisdeprivedofsufficient

oxygenandglucose.Ifcellrespirationceasesinneurons,theybecomeirreparablydamaged

anddie.Strokesvarygreatlyinseverity.

Manyaresominorthatthepatienthardlynotices.Aboutone-thirdofsufferersfrommajor

strokesmakeafullrecoveryandanotherthirdsurvivebutareleftwithadisability.Inmany

cases,recoveryfromstrokesinvolvespartsofthebraintakingonnewfunctionsto

supplementthedamagedareas.Mostrecoveryhappensoverthefirstsixmonthsaftera

majorstrokeandmayinvolverelearningaspectsofspeechandwriting,regainingspatial

awarenessandtheabilitytocarryoutskilledphysicalactivitiessuchasdressingor

preparingfood.

10.AnnotateadiagramofembryonictissuesinXenopus,usedasananimal

model,duringneurulation.

Xenopusareagenusoffrogthatrobustembryosthatcantolerateextensivemanipulation.

Thismakesthemsuitableanimalmodelsforinvestigatingthedevelopmentalstagesof

embryogenesis.Duringneurulation,thefollowingembryonictissuesshouldbeeasily

identifiable:

1.Threegermlayers(outer=ectoderm;middle=mesoderm;inner=endoderm)

2.Ahollowcavitycalledthearchenteron(willdevelopintothedigestivetract)

3.Notochord(theflexiblerodthatstimulatesneurulation)

4.Neuraltube(developedfromtheunfoldingoftheneuralplate)

StructureandfunctionrelationshipbetweenthetissuelayersofaXenopusembryo

Transversecross-sectionofaXenopusembryo(left:micrograph;right:schematic)

DorsalDorsal

-endoderm-

VentralVentral

A.2Thehumanbrain

1.Explainhowtheanteriorpartoftheneuraltubeexpandstoformthebrain

Duringthedevelopmentofvertebrateembryos,aneuraltubeformsalongthewholeofthe

dorsalside,abovethegut,nearthesurface.Mostoftheneuraltubebecomesthespinal

cord,buttheanteriorendexpandsanddevelopsintothebrainaspartofaprocesscalled

cephalization,thedevelopmentofahead.

Thehumanbraincontainsapproximately86billionneurons.Thebrainactsasthecentral

controlcentreforthewholebody,bothdirectlyfromcranialnervesandindirectlyviathe

spinalcordandnumeroussignalmoleculescarriedbytheblood.Theadvantageofhavinga

brainisthatcommunicationbetweenthebillionsofneuronsinvolvedcanbemorerapidthan

ifcontrolcentresweremoredispersed.Themajorsensoryorgansarelocatedattheanterior

endofvertebrates:theeyes,ears,nose,andtongue.

TypesofStrokes

Hemorrhage/blood

leaksintobraintissue

EmbryonicBrainRegionsDevelopedBrainStructures

Forebrain

Midbrain??MesencephalonPartsofbrainstem

MetencephalonPonsCerebellum

Hindbrain—

MyelencephalonMedullaoblongata

Embryoat3weeksEmbryoat7weeksEmbryoat11weeks

2.Describethedifferentpartsofthebrainandtheirspecificroles

Thebrainhasregionsthataredistinguishablebytheirshape,colourorbyamicroscopic

structure.Theseregionshavedifferentroles,identifiedbyphysiologicalresearchinhumans

andothermammals.Eachpartofthebrainhasaparticularfunction,someregulating

automaticprocesses,suchasheartbeatandbalance,whileotherscontrolourphysical

coordination,speech,andabilitytoreason.

1.Thecerebralhemispheresarethelargestpartofthebrainandformthe

coordinatingcentreforlearning,memory,language,andreasoning.Theseregions

receiveinformationfromthesenseorgansandcoordinateandorganisemotor

functions.

2.Thehypothalamuscontrolstheautonomicnervoussystem.Itcoordinatesthe

endocrineandnervoussystemsbyregulatingthesecretionsofthepituitarygland.

3.Thecerebellumcoordinatesmovement,posture,andbalance.

4.Themedullaoblongata(brainstem)controlsautomaticandhomeostaticactivities

suchasbreathing,swallowing,digestion,andheartrate.

5.Thepituitaryglandhastwoparts-theposteriorlobestoresreleasethehormones

oxytocinandADHfromthehypothalamus,whiletheanteriorlobeproducesand

secretessevenhormones,includingFSHandgrowthhormone,whichregulatemany

ofthebody'sfunctions.

3.Identifypartsofthebraininaphotograph,diagram,orscanofthebrain,

includingthemedullaoblongata,cerebellum,hypothalamus,pituitarygland,

andcerebralhemispheres

rightcerebralhemisphere

----------(lefthemispherenot

hypothalamus/(

pituitary、一1

glandcerebellum

、\、medullaoblongata

|干spinalcord

CerTebralHemisphere----------/

呼二

PituitaryGland/

CerebralHemisphere—4——j-

/

屋-****</f)\\」CorpusCallosum

Hypothalamus-------

v____Cerebellum

"1.4/Ponsi

PituitaryGland/

Brainstem

?------MedullaOblongata

4.Explainhowtheautonomicnervoussystemcontrolsinvoluntaryprocessesin

thebody

Theperipheralnervoussystemcomprisesallthenervesoutsidethecentralnervoussystem.

Itisdividedintotwoparts:thevoluntaryandtheautonomicnervoussystems.Involuntary

processesarecontrolledbytheautonomicnervoussystem,usingcentresinthemedulla

oblongata.

Theautonomicnervoussystemhastwoparts:sympatheticandparasympathetic.These

oftenhavecontraryeffectsonaninvoluntaryprocess.Forexample,parasympatheticnerves

causeanincreaseinbloodowtothegutwallduringdigestionandabsorptionoffood.

Sympatheticnervescauseadecreaseinbloodowduringfastingorwhenbloodisneeded

elsewhere.

5.Outlinehowcerebralcortexformsalargerproportionofthebrain

Thecerebralcortexistheouterlayerofthecerebralhemispheres.Althoughitisonlytwoto

fourmillimetresthick,uptosixdistinctivelydifferentlayersofneuronscanbeidentifiedin

sectionsstudiedunderamicroscope.Itishavingahighlycomplexarchitectureofneurons

andprocessesthemostcomplextasksinthebrain.

Onlymammalshaveacerebralcortex.Birdsandreptileshaveregionsofthebrainthat

performasimilarrangeoffunctionsbuttheyarestructurallydifferent,withcellsarrangedin

clustersratherthanlayers.Amongthemammals,thecerebralcortexvariesinsize

considerably.Inhumans,itformsalargerproportionofthebrainthaninanyothermammal.

AutonomicControlofBodySystems

PARASYMPATHETICNERVESSYMPATHETICNERVES

**Rest&digest"/"Feed&breed''??Fightorflight,

ConstrictpupilsDilatepupils

SlowheartbeatIncreaseheartbeat

ConstrictairwaysRelaxairways

StimulatestomachactivityInhibitstomachactivity,J

InhibitglucosereleaseStimulateglucoserelease

Secrete

StimulatesexualarousalPromoteejaculation

(bothmanandwoman)&vaginalcontractions

frontallobe

occipital

lobe

temporal

lobemedulla

oblongata

cerebellum

6.Thehumancerebralcortexhasbecomeenlargedprincipallybyanincreasein

totalareawithextensivefoldingtoaccommodateitwithinthecranium

Thecerebralcortexhasbecomegreatlyenlargedduringhumanevolution,andnowcontains

moreneuronsthanthatofanyotheranimal.Therehasbeenamodestincreaseinthickness,

butthecortexisstillonlyafewmillimetresthick.Theincreaseisdueprincipallytoan

increaseintotalareaandthatnecessitatesthecortexbecomingextensivelyfoldedduring

development.

Thisissolargethatthebraincanonlybeaccommodatedinsideagreatlyenlargedcranium,

formingthedistinctiveshapeofthehumanskull.Mostofthesurfaceareaofthecerebral

cortexisinthefoldsratherthanontheoutersurface.Incontrast,miceandratshavean

unfoldedsmoothcortex,butincats,therearesomefoldsandelephantsanddolphinshave

more.Amongtheprimates,monkeysandapesshowarangeofcortexsizeanddegreeof

folding,withlargersizesinprimatesthataremorecloselyrelatedtohumans.

BrainComparison—HumanversusRat(NottoScale)

HumanBrain

smoothcerebralcortexhighlyfoldedcerebralcortex

ElephantMarmosetRhesusGorillaChimpanzeeHuman

monkey

7.Thecerebralhemispheresareresponsibleforhigher-orderfunctions.

Thecerebralhemispherescarryoutthemostcomplexofthebrain'stasks.Theseareknown

ashigher-orderfunctionsandincludelearning,memory,speech,andemotions.These

higher-orderfunctionsinvolveassociationofstimulifromdifferentsourcesincludingtheeye

andearandalsofrommemories.

Theyrelyonverycomplexnetworksofneuronsthatarestillonlypartiallyunderstoodby

neurobiologists.Themostsophisticatedthoughtprocessessuchasreasoning,decision-

makingandplanningoccurinthefrontalandprefrontallobesofthecerebralcortex.Using

thesepartsofthebrainwecanorganizeouractionsinalogicalsequence,predicttheir

outcomes,developasenseofrightandwrongandbeawareofourownexistence.

LateralizationofBrainFunction

LeftHemisphereRightHemisphere

?Sensorystimulus?Sensorystimulus

fromrightsideofbodyfromleftsideofbody

?Motorcontrolof?Motorcontrolof

rightsideofbodyleftsideofbody

?Speech,languageand?Creativity

comprehension

?Spatialability

?Analysisandcalculations

?Context/perception

?Timeandsequencing

?Recognitionoffaces,

?Recognitionofwords,placesandobjects

lettersandnumbers

8.Theleftcerebralhemispherereceivessensoryinputfromsensoryreceptorsin

therightsideofthebodyandtherightsideofthevisualfieldinbotheyesand

viceversafortherighthemisphere

Thecerebralhemispheresreceivesensoryinputsfromallthesenseorgansofthebody.For

example,signalsfromtheearpasstotheauditoryareainthetemporallobe.Signalsfrom

theleftearpasstothelefthemisphereandfromtherighteartotherighthemisphere.Inputs

fromtheskin,musclesandotherinternalorganspassviathespinalcordtothe

somatosensoryareaoftheparietallobe.

Perhapssurprisingly,theimpulsesfromeachsidecrossinthebaseofthebrainsothatthe

lefthemispherereceivesimpulsesfromtherightsideofthebodyandviceversa.Inputsfrom

theeyepasstothevisualareaintheoccipitallobe,knownasthevisualcortex.Impulses

fromtherightsideoftheeldofvisionineacheyearepassedtothevisualcortexintheleft

hemisphere,whileimpulsesfromtheleftsideoftheeldofvisionineacheyepasstothe

righthemisphere.Thisintegrationofinputsenablesthebraintojudgedistanceand

perspective.

ContralateralProcessing

VisualProcessingSensorimotorProcessing

Regionsineachofthecerebralhemispherescontrolstriated("voluntary")muscles.Themain

regionisintheposteriorpartofthefrontallobeandiscalledtheprimarymotorcortex.Inthis

region,thereisaseriesofoverlappingareasthatcontrolmusclesthroughoutthebody,from

themouthatoneendoftheprimarymotorcortextothetoesattheotherend.Theprimary

motorcortexinthelefthemispherecontrolsmuscle