Scalable architecture in mammalian brains在哺乳动物的大脑可扩展的体系结构精选文档.ppt
Optical physiology and synaptic plasticity:Shari GelberDaniel OConnorDmitry SarkisovShy ShohamMegan SullivanGayle Wittenberg,Brain scaling and evolution:Mark BurishDamon ClarkKim Hatch HarrisonHao Yuan KuehJennifer ShultzMatt WagersKrysta Wyatt,Laboratory of Sam Wang,Too many learning rules!,Abbott and Nelson,Nat.Neurosci.,CA3-CA1 synapse of hippocampus,Rich history of extracellular and single-cell recordingThe cell biology and plasticity literature is vastOne synapse per connectionHas AMPA,NMDA,mGluR,Plasticity at CA3-CA1:a separable process?,Is timing between single spikes sufficient to describe the actual learning rule?How different are the requirements for potentiation and depression?Are these full inverses of each other?How might the learning rule map to behavior?Can cell biology help clarify these issues conceptually?,Questions at the CA3-CA1 synapse,Nishiyama et al.2000 Nature 408:58480 pairings at 5 Hz Cesium pipet solution,Pike et al.1999Journal of Physiology 518:57140 pairings at 5 Hz Four epochs(10 pairings each)at 10-s intervals,Christie et al.1996Learning and Memory 3:160900 pairings at 3 HzEpochs(30-60 pairings each)at 5-s intervals,At the CA3-CA1 synapse,pairing single APs gives,LTP.,no change.,LTD.,At CA3-CA1 synapses,pairing of single spikes fails to induce potentiation,Single pre+post APs100 pairings with Dt=0-7 ms(pre before post)Pairing frequency 0.1-5 Hz,However,In Nishiyama et al.Cesium replaced Potassiumin the intracellular pipette solutionThis will-depolarize neuron-block A-type K channels in dendrite-broaden action potentials,Potassium,Cesium,Cs+,K+,pairings given at 5 Hz,Cs+,K+,can bursts of APs emulate Cs+?,LTP induction requires postsynaptic bursting,CA1 neurons fire bursts during theta oscillation,Pairings must be given at high frequency,Observations on the LTP learning rule,Potentiation requires postsynaptic burstsPairings are effective at 5 Hz(near theta)does depression have these requirements?,LTD occurs under many timing conditions,All pairings given at 5 Hz,RequirementThetaBurstingLTP yes yesLTD no no,Conclusions so far,Potentiation and depression have different general induction requirements.Potentiation:active exploration(causal,bursts,5 Hz)Depression:many conditionsDuring theta,the rule acts like a phase detector.At other times,the rule is depression-only.,Why not explore parameter space exhaustively?,because its exhausting!,Shy Shoham,Uncaging in spatial patterns:High-throughput screening of neural responses,Resolution:1 micron30,000 locations per second,Subthreshold and spiking behavior for“natural”stimulation ensembles,Now play movie athttp:/synapse.princeton.edu/sam/shoham-oconnor-movie.avi,Local amplification in dendritic branches,Strategies for separating LTD and LTP,LTD and LTP are separable,LTD is fully reversible,LTP is not fully reversible!,After being induced,LTP becomes locked in,The starting distribution of CA3-CA1 synapses,1 Hz,10 Hz,10 Hz,The CA3-CA1 learning rule,butdissectable?,Complex,Large calcium signals are evoked by co-activation of parallel fibers with the climbing fiber,