Symmetric spike timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative networks

CA3–CA3 recurrent excitatory synapses are thought to play a key role in memory storage and pattern completion. Whether the plasticity properties of these synapses are consistent with their proposed network functions remains unclear. Here, we examine the properties of spike timing-dependent plasticity (STDP) at CA3–CA3 synapses. Low-frequency pairing of excitatory postsynaptic potentials (EPSPs) and action potentials (APs) induces long-term potentiation (LTP), independent of temporal order. The STDP curve is symmetric and broad (half-width ∼150 ms). Consistent with these STDP induction properties, AP–EPSP sequences lead to supralinear summation of spine [Ca2+] transients. Furthermore, afterdepolarizations (ADPs) following APs efficiently propagate into dendrites of CA3 pyramidal neurons, and EPSPs summate with dendritic ADPs. In autoassociative network models, storage and recall are more robust with symmetric than with asymmetric STDP rules. Thus, a specialized STDP induction rule allows reliable storage and recall of information in the hippocampal CA3 network.

[1]  D. W. In memory of ... , 1963, Science.

[2]  D Marr,et al.  Simple memory: a theory for archicortex. , 1971, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[3]  J J Hopfield,et al.  Neural networks and physical systems with emergent collective computational abilities. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[4]  R. Miles,et al.  Excitatory synaptic interactions between CA3 neurones in the guinea‐pig hippocampus. , 1986, The Journal of physiology.

[5]  B. McNaughton,et al.  Hippocampal synaptic enhancement and information storage within a distributed memory system , 1987, Trends in Neurosciences.

[6]  R. Nicoll,et al.  Comparison of two forms of long-term potentiation in single hippocampal neurons. , 1990, Science.

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

[8]  John Robinson,et al.  Statistical analysis of the dynamics of a sparse associative memory , 1992, Neural Networks.

[9]  P. Somogyi,et al.  The hippocampal CA3 network: An in vivo intracellular labeling study , 1994, The Journal of comparative neurology.

[10]  E. Rolls,et al.  Computational analysis of the role of the hippocampus in memory , 1994, Hippocampus.

[11]  Max R. Bennett,et al.  Dynamics of the CA3 pyramidal neuron autoassociative memory network in the hippocampus. , 1994, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[12]  H. Shinozaki,et al.  Activation of metabotropic glutamate receptor type 2/3 suppresses transmission at rat hippocampal mossy fibre synapses. , 1996, The Journal of physiology.

[13]  K. I. Blum,et al.  Functional significance of long-term potentiation for sequence learning and prediction. , 1996, Cerebral cortex.

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

[15]  D. Johnston,et al.  A Synaptically Controlled, Associative Signal for Hebbian Plasticity in Hippocampal Neurons , 1997, Science.

[16]  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.

[17]  D. Debanne,et al.  Long‐term synaptic plasticity between pairs of individual CA3 pyramidal cells in rat hippocampal slice cultures , 1998, The Journal of physiology.

[18]  J. Lisman Relating Hippocampal Circuitry to Function Recall of Memory Sequences by Reciprocal Dentate–CA3 Interactions , 1999, Neuron.

[19]  V. Han,et al.  Reversible Associative Depression and Nonassociative Potentiation at a Parallel Fiber Synapse , 2000, Neuron.

[20]  P. Jonas,et al.  Associative Long-Term Depression in the Hippocampus Is Dependent on Postsynaptic N-Type Ca2+ Channels , 2000, The Journal of Neuroscience.

[21]  M. Häusser,et al.  Dendritic coincidence detection of EPSPs and action potentials , 2001, Nature Neuroscience.

[22]  P. Pavlidis,et al.  Pair Recordings Reveal All-Silent Synaptic Connections and the Postsynaptic Expression of Long-Term Potentiation , 2001, Neuron.

[23]  M. Häusser,et al.  Differential shunting of EPSPs by action potentials. , 2001, Science.

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

[25]  M. Quirk,et al.  Requirement for Hippocampal CA3 NMDA Receptors in Associative Memory Recall , 2002, Science.

[26]  K. Svoboda,et al.  Facilitation at single synapses probed with optical quantal analysis , 2002, Nature Neuroscience.

[27]  J. Lacaille,et al.  Depolarization-Induced Long-Term Depression at Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses , 2003, The Journal of Neuroscience.

[28]  S. Nelson,et al.  Homeostatic plasticity in the developing nervous system , 2004, Nature Reviews Neuroscience.

[29]  P. Jonas,et al.  Kinetics of Mg2+ unblock of NMDA receptors: implications for spike‐timing dependent synaptic plasticity , 2004, The Journal of physiology.

[30]  D. Ulrich,et al.  Firing Mode-Dependent Synaptic Plasticity in Rat Neocortical Pyramidal Neurons , 2004, The Journal of Neuroscience.

[31]  Nelson Spruston,et al.  R-Type Calcium Channels Contribute to Afterdepolarization and Bursting in Hippocampal CA1 Pyramidal Neurons , 2005, The Journal of Neuroscience.

[32]  Y. Dan,et al.  Spike-timing-dependent synaptic plasticity depends on dendritic location , 2005, Nature.

[33]  J. Glowinski,et al.  Bidirectional Activity-Dependent Plasticity at Corticostriatal Synapses , 2005, The Journal of Neuroscience.

[34]  Johannes J. Letzkus,et al.  Learning Rules for Spike Timing-Dependent Plasticity Depend on Dendritic Synapse Location , 2006, The Journal of Neuroscience.

[35]  Anthony N. Burkitt,et al.  A review of the integrate-and-fire neuron model: II. Inhomogeneous synaptic input and network properties , 2006, Biological Cybernetics.

[36]  Anthony N. Burkitt,et al.  A Review of the Integrate-and-fire Neuron Model: I. Homogeneous Synaptic Input , 2006, Biological Cybernetics.

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

[38]  P. J. Sjöström,et al.  A Cooperative Switch Determines the Sign of Synaptic Plasticity in Distal Dendrites of Neocortical Pyramidal Neurons , 2006, Neuron.

[39]  R. Huganir,et al.  Developmental Expression of Ca2+-Permeable AMPA Receptors Underlies Depolarization-Induced Long-Term Depression at Mossy Fiber–CA3 Pyramid Synapses , 2007, The Journal of Neuroscience.

[40]  R. Kesner Behavioral functions of the CA3 subregion of the hippocampus. , 2007, Learning & memory.

[41]  N. Spruston,et al.  Dendritic D‐type potassium currents inhibit the spike afterdepolarization in rat hippocampal CA1 pyramidal neurons , 2007, The Journal of physiology.

[42]  Johannes J. Letzkus,et al.  Dendritic mechanisms controlling spike-timing-dependent synaptic plasticity , 2007, Trends in Neurosciences.

[43]  M. Poo,et al.  Spike-Timing-Dependent Plasticity of Neocortical Excitatory Synapses on Inhibitory Interneurons Depends on Target Cell Type , 2007, The Journal of Neuroscience.

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

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

[46]  J. O’Neill,et al.  Reactivation of experience-dependent cell assembly patterns in the hippocampus , 2008, Nature Neuroscience.

[47]  Jon T. Brown,et al.  Activity‐dependent depression of the spike after‐depolarization generates long‐lasting intrinsic plasticity in hippocampal CA3 pyramidal neurons , 2009, The Journal of physiology.

[48]  G. Buzsáki,et al.  Axonal morphometry of hippocampal pyramidal neurons semi-automatically reconstructed after in vivo labeling in different CA3 locations , 2011, Brain Structure and Function.

[49]  I. Ial,et al.  Nature Communications , 2010, Nature Cell Biology.

[50]  R. Tsien,et al.  Heterogeneous Reallocation of Presynaptic Efficacy in Recurrent Excitatory Circuits Adapting to Inactivity , 2011, Nature Neuroscience.

[51]  Johannes E. Schindelin,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

[52]  D. Feldman The Spike-Timing Dependence of Plasticity , 2012, Neuron.

[53]  Peter Jonas,et al.  Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons , 2012, Nature Neuroscience.

[54]  S. Vicini,et al.  Mossy Fiber-CA3 Synapses Mediate Homeostatic Plasticity in Mature Hippocampal Neurons , 2013, Neuron.

[55]  Benjamin D. Philpot,et al.  Synapse-Specific Control of Experience-Dependent Plasticity by Presynaptic NMDA Receptors , 2014, Neuron.

[56]  S. Sikdar,et al.  Depression biased non‐Hebbian spike‐timing‐dependent synaptic plasticity in the rat subiculum , 2014, The Journal of physiology.

[57]  Alois Schlögl,et al.  Stimfit: quantifying electrophysiological data with Python , 2013, Front. Neuroinform..

[58]  W. Schultz,et al.  Retroactive modulation of spike timing-dependent plasticity by dopamine , 2015, eLife.