Physiol Rev 86 1033 1048 2006 doi 10 1152 physrev 00030 2005 Spike Timing Dependent Plasticity From Synapse to Perception Yang Dan and Mu Ming Poo Physiol Rev 86 1033 1048 2006 doi 10 1152 physrev 00030 2005 Spike Timing Dependent Plasticity From Synapse to Perception You might find this additional information useful This article cites 118 articles 43 of which you can access free at http physrev physiology org cgi content full 86 3 1033 BIBL YANG DAN AND MU MING POO Medline items on this article s topics can be found at http highwire stanford edu lists artbytopic dtl on the following topics Physiology Dendrites Physiology Neuronal Excitability Veterinary Science Long Term Depression Physiology Long Term Potentiation Physiology Neural Circuit Physiology Humans This information is current as of January 4 2007 I Introduction II Cellular Mechanisms Underlying Synaptic Spike Timing Dependent Plasticity A LTP window B LTD window C Modulation of STDP by inhibitory inputs III Spike Timing Dependent Plasticity With Complex Spatiotemporal Activity Patterns A Dependence on dendritic location B Complex spike trains IV Spike Timing Dependent Plasticity in Vivo A Electrical stimulation B Sensory stimulation C Natural stimuli D Persistence of STDP in vivo V Nonsynaptic Aspects of Spike Timing Dependent Plasticity A STDP of intrinsic neuronal excitability B STDP of local dendritic excitability and synaptic integration VI Spread of Synaptic Spike Timing Dependent Plasticity in Neural Circuits A Heterosynaptic effects of LTP LTD induction B Spread of LTP LTD in cell culture C Spread of LTP LTD in vivo VII Concluding Remarks Dan Yang and Mu Ming Poo Spike Timing Dependent Plasticity From Synapse to Perception Physiol Rev 86 1033 1048 2006 doi 10 1152 physrev 00030 2005 Information in the nervous system may be carried by both the rate and timing of neuronal spikes Recent findings of spike timing dependent plasticity STDP have fueled the interest in the potential roles of spike timing in processing and storage of information in neural circuits Induction of long term potentiation LTP and long term depression LTD in a variety of in vitro and in vivo systems has been shown to depend on the temporal order of pre and postsynaptic spiking Spike timing dependent modification of neuronal excitability and dendritic integration was also observed Such STDP at the synaptic and cellular level is likely to play important roles in activity induced functional changes in neuronal receptive fields and human perception I INTRODUCTION Since the discovery of persistent enhancement of synaptic transmission by tetanic stimulation in the hippocampus 14 a phenomenon now generally referred to as long term potentiation LTP the study of activitydependent synaptic plasticity has become one of the most active areas in neurobiology 66 68 Two features of LTP the associativity and input specificity match the properties of some forms of learning and memory sugPhysiological Reviews provides state of the art coverage of timely issues in the physiological and biomedical sciences It is published quarterly in January April July and October by the American Physiological Society 9650 Rockville Pike Bethesda MD 20814 3991 Copyright 2005 by the American Physiological Society ISSN 0031 9333 ESSN 1522 1210 Visit our website at http www the aps org 1033 1034 1035 1035 1036 1036 1036 1037 1038 1038 1039 1039 1041 1042 1042 1043 1043 1043 1044 1045 1045 Downloaded from physrev physiology org on January 4 2007 Additional material and information about Physiological Reviews can be found at http www the aps org publications prv Downloaded from physrev physiology org on January 4 2007 Updated information and services including high resolution figures can be found at http physrev physiology org cgi content full 86 3 1033 Division of Neurobiology Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute University of California Berkeley California www prv org gesting that LTP may underlie such cognitive functions Traditionally LTP is induced by high frequency presynaptic stimulation or by pairing low frequency stimulation with postsynaptic depolarization Prolonged low frequency stimulation was also found to induce long term depression LTD 53 77 Thus synaptic efficacy can be modified in a bidirectional manner In studying the temporal specificity of associative synaptic modification in the hippocampus a region known to be important for memory formation Levy and 0031 9333 06 18 00 Copyright 2006 the American Physiological Society 1033 1034 Physiol Rev VOL TABLE II CELLULAR MECHANISMS UNDERLYING SYNAPTIC SPIKE TIMING DEPENDENT PLASTICITY In conventional protocols using steady postsynaptic depolarization high frequency presynaptic stimulation induces LTP and low frequency stimulation induces LTD but in STDP low frequency stimulation can be used to induce both LTP and LTD While in both types of protocols activation of N methyl D aspartate NMDA subtype of glutamate receptors NMDARs e g Refs 13 24 65 67 119 and elevation of postsynaptic Ca2 level are required the effectiveness of postsynaptic spiking and steady depolarization in achieving the required Ca2 level is likely to be different This may account for the higher efficiency of the spike timing protocol in long term modification of excitatory synapses in hippocampal cultures 13 and midbrain slices 60 The NMDARs are largely blocked by Mg2 at hyperpolarized membrane potentials but the block can be relieved by depolarization 69 83 leading to the idea that the NMDAR serves as the coincidence detector for pre post activity For LTP and LTD induced by conventional protocols different cascades of signaling events are set in motion by high and low level postsynaptic Ca2 elevation respectively 66 Does the conventional Ca2 based model of LTP LTD also explain the temporally asymmetric STDP One would expect that pre post spiking leads to a brief high level Ca2 influx due to effective activation of NMDARs by postsynaptic spiking while post pre spiking leads to a low level Ca2 rise due to the limited extent of NMDAR activation by the afterdepolarization associated with the postsynaptic action potential AP Fluorescence Ca2 imaging studies indeed demonstrated that Ca2 influx through NMDARs and voltage dependent Ca2 channels VDCCs exhibits supralinear summation with pre post spiking and sublinear summation with post pre spiking 56 79 In support of this Ca2 model for STDP pre post spiking under partial