Spike Timing Dependent Plasticity: A Consequence of More Fundamental Learning Rules

Spike timing dependent plasticity (STDP) is a phenomenon in which the precise timing of spikes affects the sign and magnitude of changes in synaptic strength. STDP is often interpreted as the comprehensive learning rule for a synapse – the “first law” of synaptic plasticity. This interpretation is made explicit in theoretical models in which the total plasticity produced by complex spike patterns results from a superposition of the effects of all spike pairs. Although such models are appealing for their simplicity, they can fail dramatically. For example, the measured single-spike learning rule between hippocampal CA3 and CA1 pyramidal neurons does not predict the existence of long-term potentiation one of the best-known forms of synaptic plasticity. Layers of complexity have been added to the basic STDP model to repair predictive failures, but they have been outstripped by experimental data. We propose an alternate first law: neural activity triggers changes in key biochemical intermediates, which act as a more direct trigger of plasticity mechanisms. One particularly successful model uses intracellular calcium as the intermediate and can account for many observed properties of bidirectional plasticity. In this formulation, STDP is not itself the basis for explaining other forms of plasticity, but is instead a consequence of changes in the biochemical intermediate, calcium. Eventually a mechanism-based framework for learning rules should include other messengers, discrete change at individual synapses, spread of plasticity among neighboring synapses, and priming of hidden processes that change a synapse's susceptibility to future change. Mechanism-based models provide a rich framework for the computational representation of synaptic plasticity.

[1]  G. Laurent,et al.  Hebbian STDP in mushroom bodies facilitates the synchronous flow of olfactory information in locusts , 2007, Nature.

[2]  Michael Brecht,et al.  Map Plasticity in Somatosensory Cortex , 2005, Science.

[3]  W. Levy,et al.  Temporal contiguity requirements for long-term associative potentiation/depression in the hippocampus , 1983, Neuroscience.

[4]  J. Csicsvari,et al.  Firing rate and theta‐phase coding by hippocampal pyramidal neurons during ‘space clamping’ , 1999, The European journal of neuroscience.

[5]  J. J. Hopfield,et al.  Pattern recognition computation using action potential timing for stimulus representation , 1995, Nature.

[6]  Murtaza Z Mogri,et al.  Targeting and Readout Strategies for Fast Optical Neural Control In Vitro and In Vivo , 2007, The Journal of Neuroscience.

[7]  B. Sakmann,et al.  Spine Ca2+ Signaling in Spike-Timing-Dependent Plasticity , 2006, The Journal of Neuroscience.

[8]  T. Sejnowski,et al.  Storing covariance with nonlinearly interacting neurons , 1977, Journal of mathematical biology.

[9]  G. M. Rose,et al.  Induction of hippocampal long-term potentiation using physiologically patterned stimulation , 1986, Neuroscience Letters.

[10]  Gary Lynch,et al.  Role of N-methyl-D-aspartate receptors in the induction of synaptic potentiation by burst stimulation patterned after the hippocampal θ-rhythm , 1988, Brain Research.

[11]  J J Hopfield,et al.  Neurons with graded response have collective computational properties like those of two-state neurons. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[12]  W. Singer,et al.  Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex , 1990, Nature.

[13]  W. Gerstner,et al.  Connectivity reflects coding: a model of voltage-based STDP with homeostasis , 2010, Nature Neuroscience.

[14]  S. Wang,et al.  Order-Dependent Coincidence Detection in Cerebellar Purkinje Neurons at the Inositol Trisphosphate Receptor , 2008, The Journal of Neuroscience.

[15]  V. Han,et al.  Synaptic plasticity in a cerebellum-like structure depends on temporal order , 1997, Nature.

[16]  D. Rumelhart Parallel Distributed Processing Volume 1: Foundations , 1987 .

[17]  D. J. Felleman,et al.  Distributed hierarchical processing in the primate cerebral cortex. , 1991, Cerebral cortex.

[18]  A. Kirkwood,et al.  Neuromodulators Control the Polarity of Spike-Timing-Dependent Synaptic Plasticity , 2007, Neuron.

[19]  H. Abarbanel,et al.  Dynamical model of long-term synaptic plasticity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Karel Svoboda,et al.  Locally dynamic synaptic learning rules in pyramidal neuron dendrites , 2007, Nature.

[21]  L. Abbott,et al.  Synaptic plasticity: taming the beast , 2000, Nature Neuroscience.

[22]  M. Poo,et al.  Calcium stores regulate the polarity and input specificity of synaptic modification , 2000, Nature.

[23]  W. N. Ross,et al.  Inositol 1 , 4 , 5-Trisphosphate ( IP 3 )-Mediated Ca 2 1 Release Evoked by Metabotropic Agonists and Backpropagating Action Potentials in Hippocampal CA 1 Pyramidal Neurons , 2000 .

[24]  E. Capaldi,et al.  The organization of behavior. , 1992, Journal of applied behavior analysis.

[25]  E. Bienenstock,et al.  Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  M. Sakurai,et al.  Differential induction of LTP and LTD is not determined solely by instantaneous calcium concentration: an essential involvement of a temporal factor , 2001, The European journal of neuroscience.

[27]  Nicolas Brunel,et al.  STDP in a Bistable Synapse Model Based on CaMKII and Associated Signaling Pathways , 2007, PLoS Comput. Biol..

[28]  Rajesh P. N. Rao,et al.  Spike-Timing-Dependent Hebbian Plasticity as Temporal Difference Learning , 2001, Neural Computation.

[29]  D. Feldman,et al.  Timing-Based LTP and LTD at Vertical Inputs to Layer II/III Pyramidal Cells in Rat Barrel Cortex , 2000, Neuron.

[30]  A. Artola,et al.  Synaptic Activity Modulates the Induction of Bidirectional Synaptic Changes in Adult Mouse Hippocampus , 2000, The Journal of Neuroscience.

[31]  Richard Hans Robert Hahnloser,et al.  Spike-Time-Dependent Plasticity and Heterosynaptic Competition Organize Networks to Produce Long Scale-Free Sequences of Neural Activity , 2010, Neuron.

[32]  Y. Dan,et al.  Spike-timing-dependent synaptic modification induced by natural spike trains , 2002, Nature.

[33]  D. Feldman,et al.  Long-term depression induced by sensory deprivation during cortical map plasticity in vivo , 2003, Nature Neuroscience.

[34]  H. Shouval,et al.  Stochastic properties of synaptic transmission affect the shape of spike time-dependent plasticity curves. , 2005, Journal of neurophysiology.

[35]  P. J. Sjöström,et al.  Rate, Timing, and Cooperativity Jointly Determine Cortical Synaptic Plasticity , 2001, Neuron.

[36]  J. Konorski Conditioned reflexes and neuron organization. , 1948 .

[37]  Matthew E Larkum,et al.  Synaptic clustering by dendritic signalling mechanisms , 2008, Current Opinion in Neurobiology.

[38]  Y. Dan,et al.  Contribution of individual spikes in burst-induced long-term synaptic modification. , 2006, Journal of neurophysiology.

[39]  F. Engert,et al.  Synapse specificity of long-term potentiation breaks down at short distances , 1997, Nature.

[40]  Karel Svoboda,et al.  Plasticity of calcium channels in dendritic spines , 2003, Nature Neuroscience.

[41]  Yitzhak Schiller,et al.  NMDA receptor-mediated dendritic spikes and coincident signal amplification , 2001, Current Opinion in Neurobiology.

[42]  Nace L. Golding,et al.  Dendritic spikes as a mechanism for cooperative long-term potentiation , 2002, Nature.

[43]  O. Paulsen,et al.  Rapid report: postsynaptic bursting is essential for 'Hebbian' induction of associative long-term potentiation at excitatory synapses in rat hippocampus. , 1999, The Journal of physiology.

[44]  R. Nicoll,et al.  Ca2+ Signaling Requirements for Long-Term Depression in the Hippocampus , 1996, Neuron.

[45]  Samuel S.-H. Wang,et al.  Targeting and Excitation of Photoactivatable Molecules: Design Considerations for Neurophysiology Experiments , 2011 .

[46]  M. Bear,et al.  Metaplasticity: the plasticity of synaptic plasticity , 1996, Trends in Neurosciences.

[47]  L. Abbott,et al.  Competitive Hebbian learning through spike-timing-dependent synaptic plasticity , 2000, Nature Neuroscience.

[48]  Carson C. Chow,et al.  Calcium time course as a signal for spike-timing-dependent plasticity. , 2005, Journal of neurophysiology.

[49]  J. Hopfield,et al.  All-or-none potentiation at CA3-CA1 synapses. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[50]  Haim Sompolinsky,et al.  Learning Input Correlations through Nonlinear Temporally Asymmetric Hebbian Plasticity , 2003, The Journal of Neuroscience.

[51]  D. Johnston,et al.  Active dendrites, potassium channels and synaptic plasticity. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[52]  R. Malenka,et al.  Mechanisms underlying induction of homosynaptic long-term depression in area CA1 of the hippocampus , 1992, Neuron.

[53]  R. Kempter,et al.  Hebbian learning and spiking neurons , 1999 .

[54]  D. Amit,et al.  Model of global spontaneous activity and local structured activity during delay periods in the cerebral cortex. , 1997, Cerebral cortex.

[55]  Wulfram Gerstner,et al.  SPIKING NEURON MODELS Single Neurons , Populations , Plasticity , 2002 .

[56]  Jeffrey P. Gavornik,et al.  Effect of stochastic synaptic and dendritic dynamics on synaptic plasticity in visual cortex and hippocampus. , 2007, Journal of neurophysiology.

[57]  Paul Antoine Salin,et al.  Cyclic AMP Mediates a Presynaptic Form of LTP at Cerebellar Parallel Fiber Synapses , 1996, Neuron.

[58]  L. Cooper,et al.  Synaptic homeostasis and input selectivity follow from a calcium-dependent plasticity model. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[59]  M. Mehta Cooperative LTP can map memory sequences on dendritic branches , 2004, Trends in Neurosciences.

[60]  J L van Hemmen,et al.  Intracellular Ca2+ stores can account for the time course of LTP induction: a model of Ca2+ dynamics in dendritic spines. , 1995, Journal of neurophysiology.

[61]  E. Kandel,et al.  Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. , 1993, Science.

[62]  T. Bliss,et al.  Long‐lasting potentiation of synaptic transmission in the dentate area of the unanaesthetized rabbit following stimulation of the perforant path , 1973, The Journal of physiology.

[63]  S. Wang,et al.  Graded bidirectional synaptic plasticity is composed of switch-like unitary events. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[64]  David W. Nauen,et al.  Coactivation and timing-dependent integration of synaptic potentiation and depression , 2005, Nature Neuroscience.

[65]  Sachin S Talathi,et al.  Synaptic plasticity with discrete state synapses. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[66]  James J Knierim,et al.  A biophysical model of synaptic plasticity and metaplasticity can account for the dynamics of the backward shift of hippocampal place fields. , 2008, Journal of neurophysiology.

[67]  W. N. Ross,et al.  Calcium transients evoked by climbing fiber and parallel fiber synaptic inputs in guinea pig cerebellar Purkinje neurons. , 1992, Journal of neurophysiology.

[68]  G. Bi,et al.  Gain in sensitivity and loss in temporal contrast of STDP by dopaminergic modulation at hippocampal synapses , 2009, Proceedings of the National Academy of Sciences.

[69]  Wade G. Regehr,et al.  Timing dependence of the induction of cerebellar LTD , 2008, Neuropharmacology.

[70]  S. Wang,et al.  Dissection of bidirectional synaptic plasticity into saturable unidirectional processes. , 2005, Journal of neurophysiology.

[71]  Ken-ichi Hara,et al.  A generalized Hebbian rule for activity-dependent synaptic modifications , 2000, Neural Networks.

[72]  M. Bear,et al.  Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[73]  G. Stent A physiological mechanism for Hebb's postulate of learning. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[74]  Mark C. W. van Rossum,et al.  Stable Hebbian Learning from Spike Timing-Dependent Plasticity , 2000, The Journal of Neuroscience.

[75]  J. Lisman,et al.  A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[76]  L. Abbott,et al.  Cascade Models of Synaptically Stored Memories , 2005, Neuron.

[77]  S. Wang,et al.  Malleability of Spike-Timing-Dependent Plasticity at the CA3–CA1 Synapse , 2006, The Journal of Neuroscience.

[78]  Karel Svoboda,et al.  Subcellular Dynamics of Type II PKA in Neurons , 2009, Neuron.

[79]  Eugene M. Izhikevich,et al.  Relating STDP to BCM , 2003, Neural Computation.

[80]  G. Augustine,et al.  Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[81]  J. Kerr,et al.  Dopamine Receptor Activation Is Required for Corticostriatal Spike-Timing-Dependent Plasticity , 2008, The Journal of Neuroscience.

[82]  F. Gonon Prolonged and Extrasynaptic Excitatory Action of Dopamine Mediated by D1 Receptors in the Rat Striatum In Vivo , 1997, The Journal of Neuroscience.

[83]  J. Lisman,et al.  A Model of Synaptic Memory A CaMKII/PP1 Switch that Potentiates Transmission by Organizing an AMPA Receptor Anchoring Assembly , 2001, Neuron.

[84]  L. Cooper,et al.  A unified model of NMDA receptor-dependent bidirectional synaptic plasticity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[85]  J. Zhu,et al.  Synaptic AMPA Receptor Exchange Maintains Bidirectional Plasticity , 2006, Neuron.

[86]  Alex M. Andrew,et al.  Spiking Neuron Models: Single Neurons, Populations, Plasticity , 2003 .

[87]  Vanessa A. Bender,et al.  Two Coincidence Detectors for Spike Timing-Dependent Plasticity in Somatosensory Cortex , 2006, The Journal of Neuroscience.

[88]  L. Squire CHAPTER 7 – Memory and the Brain* , 1986 .

[89]  W. Gerstner,et al.  Triplets of Spikes in a Model of Spike Timing-Dependent Plasticity , 2006, The Journal of Neuroscience.

[90]  P. J. Sjöström,et al.  Neocortical LTD via Coincident Activation of Presynaptic NMDA and Cannabinoid Receptors , 2003, Neuron.

[91]  Rishikesh Narayanan,et al.  Long-Term Potentiation in Rat Hippocampal Neurons Is Accompanied by Spatially Widespread Changes in Intrinsic Oscillatory Dynamics and Excitability , 2007, Neuron.

[92]  Henry Markram,et al.  Neural Networks with Dynamic Synapses , 1998, Neural Computation.

[93]  J. Donoghue,et al.  Plasticity of the synaptic modification range. , 2007, Journal of neurophysiology.

[94]  W. N. Ross,et al.  Inositol 1,4,5-Trisphosphate (IP3)-Mediated Ca2+ Release Evoked by Metabotropic Agonists and Backpropagating Action Potentials in Hippocampal CA1 Pyramidal Neurons , 2000, The Journal of Neuroscience.

[95]  S. Kaplan The Physiology of Thought , 1950 .

[96]  H. Markram,et al.  Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs , 1997, Science.

[97]  Karel Svoboda,et al.  Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging , 2006, Nature Neuroscience.

[98]  Philipp Slusallek,et al.  Introduction to real-time ray tracing , 2005, SIGGRAPH Courses.

[99]  D. Hubel,et al.  EFFECTS OF VISUAL DEPRIVATION ON MORPHOLOGY AND PHYSIOLOGY OF CELLS IN THE CATS LATERAL GENICULATE BODY. , 1963, Journal of neurophysiology.

[100]  Wulfram Gerstner,et al.  Tag-Trigger-Consolidation: A Model of Early and Late Long-Term-Potentiation and Depression , 2008, PLoS Comput. Biol..

[101]  G. Bi,et al.  Synaptic Modifications in Cultured Hippocampal Neurons: Dependence on Spike Timing, Synaptic Strength, and Postsynaptic Cell Type , 1998, The Journal of Neuroscience.

[102]  N. Hartell,et al.  Strong Activation of Parallel Fibers Produces Localized Calcium Transients and a Form of LTD That Spreads to Distant Synapses , 1996, Neuron.

[103]  S. Wang,et al.  Coincidence detection in single dendritic spines mediated by calcium release , 2000, Nature Neuroscience.

[104]  M. Poo,et al.  Coincident Pre- and Postsynaptic Activity Modifies GABAergic Synapses by Postsynaptic Changes in Cl− Transporter Activity , 2003, Neuron.

[105]  T. Bliss,et al.  Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path , 1973, The Journal of physiology.

[106]  W. Schultz Getting Formal with Dopamine and Reward , 2002, Neuron.

[107]  J. Cowan,et al.  A mathematical theory of the functional dynamics of cortical and thalamic nervous tissue , 1973, Kybernetik.

[108]  Wulfram Gerstner,et al.  A neuronal learning rule for sub-millisecond temporal coding , 1996, Nature.

[109]  U. Staubli,et al.  Factors regulating the reversibility of long-term potentiation , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[110]  R. Zucker,et al.  Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation. , 1999, Journal of neurophysiology.

[111]  Niraj S. Desai,et al.  Activity-dependent scaling of quantal amplitude in neocortical neurons , 1998, Nature.

[112]  Dean V. Buonomano,et al.  Mechanisms and significance of spike-timing dependent plasticity , 2002, Biological Cybernetics.

[113]  B. Sabatini,et al.  Calcium Signaling in Dendrites and Spines: Practical and Functional Considerations , 2008, Neuron.

[114]  Jackie Schiller,et al.  Spatiotemporally graded NMDA spike/plateau potentials in basal dendrites of neocortical pyramidal neurons. , 2008, Journal of neurophysiology.

[115]  E. Kandel,et al.  cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase , 1994, Cell.

[116]  E. Oja Simplified neuron model as a principal component analyzer , 1982, Journal of mathematical biology.

[117]  P. J. Sjöström,et al.  Dendritic excitability and synaptic plasticity. , 2008, Physiological reviews.