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FunctionaldissectionoftheCA3-CA1learningruleSamWangPrincetonUniversity:///~sam/Wang-STDP.pptOpticalphysiologyandsynapticplasticity:ShariGelberDanielO’ConnorDmitrySarkisovShyShohamMeganSullivanGayleWittenbergBrainscalingandevolution:MarkBurishDamonClarkKimHatchHarrisonHaoYuanKuehJenniferShultzMattWagersKrystaWyattLaboratoryofSamWangToomanylearningrules!AbbottandNelson,Nat.Neurosci.CA3-CA1synapseofhippocampusRichhistoryofextracellularandsingle-cellrecordingThecellbiologyandplasticityliteratureisvastOnesynapseperconnectionHasAMPA,NMDA,mGluR,…PlasticityatCA3-CA1:aseparableprocess?Istimingbetweensinglespikessufficienttodescribetheactuallearningrule?Howdifferentaretherequirementsforpotentiationanddepression?Arethesefullinversesofeachother?Howmightthelearningrulemaptobehavior?Cancellbiologyhelpclarifytheseissuesconceptually?QuestionsattheCA3-CA1synapseNishiyamaetal.2000Nature408:58480pairingsat5HzCesiumpipetsolutionPikeetal.1999JournalofPhysiology518:57140pairingsat5HzFourepochs(10pairingseach)at10-sintervalsChristieetal.1996LearningandMemory3:160900pairingsat3HzEpochs(30-60pairingseach)at5-sintervalsAttheCA3-CA1synapse,pairingsingleAPsgives……LTP.…nochange.…LTD.AtCA3-CA1synapses,pairingofsinglespikesfailstoinducepotentiationSinglepre+postAPs100pairingswithDt=0-7ms(prebeforepost)Pairingfrequency0.1-5HzHowever…InNishiyamaetal.

CesiumreplacedPotassium intheintracellularpipettesolutionThiswill… -depolarizeneuron -blockA-typeKchannelsindendrite -broadenactionpotentialsPotassiumCesiumCs+K+pairingsgivenat5HzCs+K+…canburstsofAPsemulateCs+?LTPinductionrequirespostsynapticburstingCA1neuronsfireburstsduringthetaoscillationPairingsmustbegivenathighfrequencyDtObservationsontheLTPlearningrulePotentiationrequirespostsynapticburstsPairingsareeffectiveat5Hz(neartheta)…doesdepressionhavetheserequirements?LTDoccursundermanytimingconditionsAllpairingsgivenat5HzRequirement Theta BurstingLTP yes yesLTD no noConclusionssofarPotentiationanddepressionhavedifferentgeneralinductionrequirements.Potentiation:activeexploration(causal,bursts,5Hz)Depression:manyconditionsDuringtheta,theruleactslikeaphasedetector.Atothertimes,theruleisdepression-only.Whynotexploreparameterspaceexhaustively?…becauseit’sexhausting!ShyShohamUncaginginspatialpatterns:High-throughputscreeningofneuralresponsesResolution:<1micron30,000locationspersecondSubthresholdandspikingbehaviorfor“natural〞stimulationensemblesNowplaymovieat:///~sam/shoham-oconnor-movie.aviLocalamplificationindendriticbranchesStrategiesforseparatingLTDandLTPLTDandLTPareseparableLTDisfullyreversibleLTPisnotfullyreversible!Afterbeinginduced,LTPbecomeslockedinThestartingdistributionofCA3-CA1synaps

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