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1、Outline 1 Thebasicconceptsoflearning memoryclassificationoflearning memorybrainstructureshostinglearning memorylearning memoryinbehavioralstudylearning memoryandneuralplasticity2 Themolecularbasisoflearning memorystudiesinAplysiastudiesinmouse LTP LTDandlongtermmemory Aplysia habituationsensitizatio
2、nassociativelearningVertebrates LTPandLTDMolecularmechanismofLTM InvertebrateNervousSystemsShowPlasticity Aplysia HabituationinAplysia Squirtsofwateronitssiphoncausesittoretractitsgill Afterrepeatedsquirts theanimalretractsthegillsless ithaslearnedthatthewaterposesnodanger atthesensorynerveendingsin
3、theskin makingthemlesssensitivetothesquirtofwater atthemuscle makingitlessresponsivetosynapticstimulationbythemotorneuron atthesynapsebetweenthesensoryneuronandthemotorneuron RepeatedelectricalstimulationofasensoryNeuronleadstoaprogressivelysmallerEPSPinthepostsynapticmotorneuron Wherethechangeunder
4、lyinghabituationoccur Wheredoesthesynapticmodificationhappen lessneurotransmitterreleasebythepresynapticaxon therearefewerquantareleasedperactionpotentialafterhabituation decreasedpostsynapticresponsivenesstothetransmitter ThesensitivityofthepostsynapticcelltoneurotransmitterdidnotchangeHabituationo
5、fthegill withdrawalreflexisassociatedwithapresynapticmodification Whyisneurotransmitterreleasereducedafterrepeatedstimulationofthesensorynerveterminal AcriticalstepistheentryofCa2 intotheterminal whichismediatedbyvoltage gatedcalciumchannels Inthenerveterminalofthesensoryneuron thesechannelsbecomepr
6、ogressivelyandpersistentlylesseffectivefollowinghabituation Despitetheapparentsimplicityofthistypeoflearning howthischangeoccursisstillunknown SensitizationoftheGill WithdrawalReflex abriefelectricalshockappliedtotheheadofAplysiaresultsinexaggeratedgillwithdrawalinresponsetostimulationofthesiphon Th
7、emolecularmechanismofsensitization L29release5 HTinresponsetoheadshock5 HTbind5 HTreceptorandactivateG proteincoupledadenylylcyclaseinsensoryaxonterminal CyclicAMPproductionactivatesproteinkinaseA PKA PKAphosphorylatepotassiumchannel causingittoclose Cont d ClosureofK channelsleadtoprolongationofpre
8、synapticactionpotentialMoreCa2 entrythroughvoltagegatedcalciumchannelsandmorequantaofneurotransmittersarereleasedMorepostsynapticglutamatereceptorscanalsoaddtotheexplanationofsensitization ConditioningoccurredonlyiftheCSprecededtheUSby 0 5second AssociativeLearninginAplysiaClassicalconditioning US a
9、strongshocktothetail CS gentlestimulationofthesiphonthatdoesnotcausearesponse Response thewithdrawalofthegill a TheUSaloneleadstoactivationofthemotorneuron viaaninterneuron notshown andtosensitizationofthesensoryinput b PairingtheCSandtheUScausesgreateractivationofadenylylcyclasethaneitherstimulusdo
10、esbyitselfbecausetheCSadmitsCa2 intothepresynapticterminal TheCa2 byinteractingwithaproteincalledcalmodulin increasestheresponseofadenylylcyclasetoG proteins Aplysia Vertebrates LTPandLTDMolecularmechanismofLTM synapticplasticityincerebellarcortexAnatomyoftheCerebellarCortexLong TermDepressionintheC
11、erebellarCortexMechanismsofCerebellarLTDsynapticplasticityinhippocampusAnatomyoftheHippocampusPropertiesofLTPinCA1MechanismsofLTPinCA1 Learningandmemoryinvertebrates Long TermDepressionintheCerebellarCortex LTD afterpairingstimulationofparallelfiberandclimbingfiber activationoftheparallelfibersalone
12、resultedinasmaller long lastingpostsynapticresponseinthePurkinjecell inferioroliveandmuscleproprioceptors Thestructureofthecerebellarcortex pontinenucleiandcerebralneocortex MechanismsofcerebellarLTD ClimbingfiberactivationdepolarizesthePurkinjecelldendrite andthenactivatevoltage gatedcalciumchannel
13、stoallowinfluxofCa2 ParallelfiberreleaseglutamatetoactivatepostsynapticAMPAreceptorandallowNa influxinPurkinjecelldendriteThereispostsynapticmetabotropicglutamatereceptorthatiscoupledviaGproteintophospholipaseCwhichcanproduceDAGtoactivatePKCPKCphosphorylateGluR2 anddecreasepostsynapticAMPAreceptors
14、LTDiscausedwhenthreeintracellularsignalsoccuratthesametime 1 arisein Ca2 iduetoclimbingfiberactivation 2 arisein Na iduetoAMPAreceptoractivation 3 activationofproteinkinaseCduetometabotropicreceptoractivation LTDcertainlyinvolvesthephosphorylationofproteins includinganAMPAreceptorsubunitcalledGluR2
15、byproteinkinaseC TheendresultisadecreaseinthenumberofAMPAreceptorchannelsinthepostsynapticmembrane LTPinHippocampalCircuits Long termpotentiation LTP astableandenduringincreaseintheeffectivenessofsynapses Somemicrocircuitsofthehippocampus Informationflowsfromtheentorhinalcortexviatheperforantpathtot
16、hedentategyrus ThedentategyrusgranulecellsemitaxonscalledmossyfibersthatsynapseonpyramidalneuronsinareaCA3 AxonsfromtheCA3neurons calledSchaffercollaterals synapseonpyramidalneuronsinareaCA1 LTPareperformedontheSchaffercollateralsynapsesontheCA1pyramidalneurons Long termpotentiationinCA1 TheresponseofaCA1neuronismonitoredastwoinputsarealternatelystimulated LTPisinducedininput1bygivingthisinputatetanus b Thegraphshowsarecordoftheexperiment Thetetanustoinput1 arrow yieldsapotentiatedresponsetostim