How Dendrites Affect Online Recognition Memory

In order to record the stream of autobiographical information that defines our unique personal history, our brains must form durable memories from single brief exposures to the patterned stimuli that impinge on them continuously throughout life. However, little is known about the computational strategies or neural mechanisms that underlie the brain's ability to perform this type of "online" learning. Based on increasing evidence that dendrites act as both signaling and learning units in the brain, we developed an analytical model that relates online recognition memory capacity to roughly a dozen dendritic, network, pattern, and task-related parameters. We used the model to determine what dendrite size maximizes storage capacity under varying assumptions about pattern density and noise level. We show that over a several-fold range of both of these parameters, and over multiple orders-of-magnitude of memory size, capacity is maximized when dendrites contain a few hundred synapses—roughly the natural number found in memory-related areas of the brain. Thus, in comparison to entire neurons, dendrites increase storage capacity by providing a larger number of better-sized learning units. Our model provides the first normative theory that explains how dendrites increase the brain’s capacity for online learning; predicts which combinations of parameter settings we should expect to find in the brain under normal operating conditions; leads to novel interpretations of an array of existing experimental results; and provides a tool for understanding which changes associated with neurological disorders, aging, or stress are most likely to produce memory deficits—knowledge that could eventually help in the design of improved clinical treatments for memory loss.

[1]  M. Gallagher,et al.  Aging, spatial learning, and total synapse number in the rat CA1 stratum radiatum , 2004, Neurobiology of Aging.

[2]  R. Tremblay,et al.  GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits , 2016, Neuron.

[3]  H. Eichenbaum,et al.  Towards a functional organization of episodic memory in the medial temporal lobe , 2012, Neuroscience & Biobehavioral Reviews.

[4]  Christina Müller,et al.  Dendritic inhibition mediated by O-LM and bistratified interneurons in the hippocampus , 2014, Front. Synaptic Neurosci..

[5]  Wen-Liang L Zhou,et al.  The decade of the dendritic NMDA spike , 2010, Journal of neuroscience research.

[6]  F. Krasne,et al.  Evidence for a computational distinction between proximal and distal neuronal inhibition. , 1992, Science.

[7]  Karim Nader,et al.  GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[8]  T. Freund,et al.  Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells , 2001, Neuroscience.

[9]  Tobias Bonhoeffer,et al.  Activity-Dependent Clustering of Functional Synaptic Inputs on Developing Hippocampal Dendrites , 2011, Neuron.

[10]  M. Carandini,et al.  Normalization as a canonical neural computation , 2011, Nature Reviews Neuroscience.

[11]  U. Frey,et al.  Synaptic tagging and long-term potentiation , 1997, Nature.

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

[13]  Susumu Tonegawa,et al.  The Dendritic Branch Is the Preferred Integrative Unit for Protein Synthesis-Dependent LTP , 2011, Neuron.

[14]  H. Seung,et al.  Robust persistent neural activity in a model integrator with multiple hysteretic dendrites per neuron. , 2003, Cerebral cortex.

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

[16]  R. Silver,et al.  Shunting Inhibition Modulates Neuronal Gain during Synaptic Excitation , 2003, Neuron.

[17]  Paul A. Rhodes,et al.  The Properties and Implications of NMDA Spikes in Neocortical Pyramidal Cells , 2006, The Journal of Neuroscience.

[18]  D. Willshaw,et al.  Short-term Associative Memory , 2002 .

[19]  Bartlett W. Mel,et al.  Cortical rewiring and information storage , 2004, Nature.

[20]  Bartlett W. Mel,et al.  Computational subunits in thin dendrites of pyramidal cells , 2004, Nature Neuroscience.

[21]  Karel Svoboda,et al.  Activity-Dependent Plasticity of the NMDA-Receptor Fractional Ca2+ Current , 2007, Neuron.

[22]  D. Johnston,et al.  Temporal synchrony and gamma to theta power conversion in the dendrites of CA1 pyramidal neurons , 2013, Nature Neuroscience.

[23]  Idan Segev,et al.  Principles Governing the Operation of Synaptic Inhibition in Dendrites , 2012, Neuron.

[24]  Bartlett W. Mel,et al.  Pyramidal Neuron as Two-Layer Neural Network , 2003, Neuron.

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

[26]  Bartlett W. Mel NMDA-Based Pattern Discrimination in a Modeled Cortical Neuron , 1992, Neural Computation.

[27]  Stanislas Dehaene,et al.  Networks of Formal Neurons and Memory Palimpsests , 1986 .

[28]  J. Magee,et al.  Integrative Properties of Radial Oblique Dendrites in Hippocampal CA1 Pyramidal Neurons , 2006, Neuron.

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

[30]  Bartlett W. Mel,et al.  An Augmented Two-Layer Model Captures Nonlinear Analog Spatial Integration Effects in Pyramidal Neuron Dendrites , 2014, Proceedings of the IEEE.

[31]  Bartlett W. Mel,et al.  Translation-Invariant Orientation Tuning in Visual “Complex” Cells Could Derive from Intradendritic Computations , 1998, The Journal of Neuroscience.

[32]  N. Spruston,et al.  Conditional dendritic spike propagation following distal synaptic activation of hippocampal CA1 pyramidal neurons , 2005, Nature Neuroscience.

[33]  Emilio Salinas,et al.  Gain Modulation A Major Computational Principle of the Central Nervous System , 2000, Neuron.

[34]  J. Magee,et al.  Structured Synaptic Connectivity between Hippocampal Regions , 2014, Neuron.

[35]  Wolfgang Maass,et al.  Branch-Specific Plasticity Enables Self-Organization of Nonlinear Computation in Single Neurons , 2011, The Journal of Neuroscience.

[36]  Roberto Malinow,et al.  Compartmentalized versus Global Synaptic Plasticity on Dendrites Controlled by Experience , 2011, Neuron.

[37]  L. Abbott,et al.  Limits on the memory storage capacity of bounded synapses , 2007, Nature Neuroscience.

[38]  Dominique Muller,et al.  LTP Promotes a Selective Long-Term Stabilization and Clustering of Dendritic Spines , 2008, PLoS biology.

[39]  Bertalan K. Andrásfalvy,et al.  Location-dependent synaptic plasticity rules by dendritic spine cooperativity , 2016, Nature Communications.

[40]  Y. Dan,et al.  An arithmetic rule for spatial summation of excitatory and inhibitory inputs in pyramidal neurons , 2009, Proceedings of the National Academy of Sciences.

[41]  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.

[42]  Norio Matsuki,et al.  Locally Synchronized Synaptic Inputs , 2012, Science.

[43]  J. Schiller,et al.  Active properties of neocortical pyramidal neuron dendrites. , 2013, Annual review of neuroscience.

[44]  J. Schiller,et al.  A Novel Form of Local Plasticity in Tuft Dendrites of Neocortical Somatosensory Layer 5 Pyramidal Neurons , 2016, Neuron.

[45]  F. Helmchen,et al.  Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells , 2016, Nature Communications.

[46]  A. Borst,et al.  Dendritic processing of synaptic information by sensory interneurons , 1994, Trends in Neurosciences.

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

[48]  Daniel J. Amit,et al.  Learning in Neural Networks with Material Synapses , 1994, Neural Computation.

[49]  M. Häusser,et al.  The single dendritic branch as a fundamental functional unit in the nervous system , 2010, Current Opinion in Neurobiology.

[50]  N. Spruston,et al.  Dendritic spikes induce single-burst long-term potentiation , 2007, Proceedings of the National Academy of Sciences.

[51]  Nelson Spruston,et al.  Distance-Dependent Differences in Synapse Number and AMPA Receptor Expression in Hippocampal CA1 Pyramidal Neurons , 2006, Neuron.

[52]  Kenji Morita Possible Role of Dendritic Compartmentalization in the Spatial Working Memory Circuit , 2008, The Journal of Neuroscience.

[53]  Rafal Bogacz,et al.  Comparison of computational models of familiarity discrimination in the perirhinal cortex , 2003, Hippocampus.

[54]  Yu Tian Wang,et al.  Blocking Synaptic Removal of GluA2-Containing AMPA Receptors Prevents the Natural Forgetting of Long-Term Memories , 2016, The Journal of Neuroscience.

[55]  Rafal Bogacz,et al.  Model of Familiarity Discrimination in the Perirhinal Cortex , 2004, Journal of Computational Neuroscience.

[56]  Bartlett W. Mel,et al.  Location-Dependent Excitatory Synaptic Interactions in Pyramidal Neuron Dendrites , 2012, PLoS Comput. Biol..

[57]  T. Poggio,et al.  Retinal ganglion cells: a functional interpretation of dendritic morphology. , 1982, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[58]  Jackie Schiller,et al.  Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo , 2012, Nature.

[59]  Judit K. Makara,et al.  Experience-dependent compartmentalized dendritic plasticity in rat hippocampal CA1 pyramidal neurons , 2009, Nature Neuroscience.

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

[61]  Paul F. M. J. Verschure,et al.  A Signature of Attractor Dynamics in the CA3 Region of the Hippocampus , 2014, PLoS Comput. Biol..

[62]  Benjamin Sivyer,et al.  Direction selectivity is computed by active dendritic integration in retinal ganglion cells , 2013, Nature Neuroscience.

[63]  I Segev,et al.  Untangling dendrites with quantitative models. , 2000, Science.

[64]  M. Häusser,et al.  Dendritic Discrimination of Temporal Input Sequences in Cortical Neurons , 2010, Science.

[65]  S. Sajikumar,et al.  Identification of Compartment- and Process-Specific Molecules Required for “Synaptic Tagging” during Long-Term Potentiation and Long-Term Depression in Hippocampal CA1 , 2007, The Journal of Neuroscience.

[66]  F. Sommer,et al.  Structural Plasticity, Effectual Connectivity, and Memory in Cortex , 2016, Front. Neuroanat..

[67]  Laurenz Wiskott,et al.  Memory Storage Fidelity in the Hippocampal Circuit: The Role of Subregions and Input Statistics , 2015, PLoS Comput. Biol..

[68]  Bartlett W. Mel,et al.  Arithmetic of Subthreshold Synaptic Summation in a Model CA1 Pyramidal Cell , 2003, Neuron.

[69]  Joshua I. Sanders,et al.  Cortical interneurons that specialize in disinhibitory control , 2013, Nature.

[70]  S. Tonegawa,et al.  A clustered plasticity model of long-term memory engrams , 2006, Nature Reviews Neuroscience.

[71]  J. Diamond,et al.  NMDA Receptors Multiplicatively Scale Visual Signals and Enhance Directional Motion Discrimination in Retinal Ganglion Cells , 2016, Neuron.

[72]  Susumu Tonegawa,et al.  Conjunctive input processing drives feature selectivity in hippocampal CA1 neurons , 2015, Nature Neuroscience.

[73]  D. Tank,et al.  In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons , 1999, Nature Neuroscience.

[74]  A. Polsky,et al.  Synaptic Integration in Tuft Dendrites of Layer 5 Pyramidal Neurons: A New Unifying Principle , 2009, Science.

[75]  Judit K. Makara,et al.  Compartmentalized dendritic plasticity and input feature storage in neurons , 2008, Nature.

[76]  Bartlett W. Mel,et al.  Capacity-Enhancing Synaptic Learning Rules in a Medial Temporal Lobe Online Learning Model , 2009, Neuron.

[77]  Armin Schneider,et al.  KIBRA (KIdney/BRAin protein) regulates learning and memory and stabilizes Protein kinase Mζ , 2014, Journal of neurochemistry.

[78]  Ju Lu,et al.  REPETITIVE MOTOR LEARNING INDUCES COORDINATED FORMATION OF CLUSTERED DENDRITIC SPINES IN VIVO , 2012, Nature.

[79]  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.

[80]  Daniel A. Dombeck,et al.  Calcium transient prevalence across the dendritic arbor predicts place field properties , 2014, Nature.

[81]  Stefano Fusi,et al.  Computational principles of synaptic memory consolidation , 2016, Nature Neuroscience.

[82]  Alcino J. Silva,et al.  Synaptic clustering within dendrites: An emerging theory of memory formation , 2015, Progress in Neurobiology.

[83]  N. Grzywacz,et al.  A model of the directional selectivity circuit in retina: transformations by neurons singly and in concert , 1992 .

[84]  Srdjan D Antic,et al.  A Strict Correlation between Dendritic and Somatic Plateau Depolarizations in the Rat Prefrontal Cortex Pyramidal Neurons , 2005, The Journal of Neuroscience.

[85]  Bartlett W. Mel,et al.  Location-Dependent Effects of Inhibition on Local Spiking in Pyramidal Neuron Dendrites , 2012, PLoS Comput. Biol..

[86]  Bartlett W. Mel,et al.  Impact of Active Dendrites and Structural Plasticity on the Memory Capacity of Neural Tissue , 2001, Neuron.

[87]  W. Senn,et al.  Top-down dendritic input increases the gain of layer 5 pyramidal neurons. , 2004, Cerebral cortex.

[88]  Haishan Yao,et al.  Control of response reliability by parvalbumin-expressing interneurons in visual cortex , 2015, Nature Communications.

[89]  Bartlett W. Mel,et al.  A model for intradendritic computation of binocular disparity , 2000, Nature Neuroscience.

[90]  Günther Palm,et al.  Memory Capacities for Synaptic and Structural Plasticity G ¨ Unther Palm , 2022 .

[91]  Pentti Kanerva,et al.  Sparse Distributed Memory , 1988 .

[92]  H. Adesnik,et al.  Input normalization by global feedforward inhibition expands cortical dynamic range , 2009, Nature Neuroscience.

[93]  Domenico Tegolo,et al.  Single neuron binding properties and the magical number 7 , 2008, Hippocampus.

[94]  Christian Lohmann,et al.  Spontaneous Activity Drives Local Synaptic Plasticity In Vivo , 2015, Neuron.

[95]  Bartlett W. Mel The Clusteron: Toward a Simple Abstraction for a Complex Neuron , 1991, NIPS.

[96]  Christine Grienberger,et al.  Dendritic function in vivo , 2015, Trends in Neurosciences.

[97]  M. Hasselmo,et al.  A model for experience-dependent changes in the responses of inferotemporal neurons , 2000, Network.

[98]  B. Connors,et al.  Regenerative activity in apical dendrites of pyramidal cells in neocortex. , 1993, Cerebral cortex.

[99]  G. Shepherd,et al.  Logic operations are properties of computer-simulated interactions between excitable dendritic spines , 1987, Neuroscience.

[100]  Nelson Spruston,et al.  Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons , 2015, eLife.

[101]  Nelson Spruston,et al.  Balanced Synaptic Impact via Distance-Dependent Synapse Distribution and Complementary Expression of AMPARs and NMDARs in Hippocampal Dendrites , 2013, Neuron.

[102]  N. Spruston,et al.  Synapse Distribution Suggests a Two-Stage Model of Dendritic Integration in CA1 Pyramidal Neurons , 2009, Neuron.

[103]  Spencer L. Smith,et al.  Dendritic spikes enhance stimulus selectivity in cortical neurons in vivo , 2013, Nature.

[104]  Urit Gordon,et al.  Plasticity Compartments in Basal Dendrites of Neocortical Pyramidal Neurons , 2006, The Journal of Neuroscience.

[105]  S. Prescott,et al.  Gain control of firing rate by shunting inhibition: Roles of synaptic noise and dendritic saturation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[106]  Masahiko Watanabe,et al.  Release probability of hippocampal glutamatergic terminals scales with the size of the active zone , 2012, Nature Neuroscience.

[107]  Malcolm W. Brown,et al.  Recognition memory: What are the roles of the perirhinal cortex and hippocampus? , 2001, Nature Reviews Neuroscience.

[108]  Surya Ganguli,et al.  A memory frontier for complex synapses , 2013, NIPS.

[109]  J. Simon Wiegert,et al.  The fate of hippocampal synapses depends on the sequence of plasticity-inducing events , 2018, bioRxiv.

[110]  P. Dayan,et al.  Optimising synaptic learning rules in linear associative memories , 1991, Biological Cybernetics.

[111]  B. Sakmann,et al.  A new cellular mechanism for coupling inputs arriving at different cortical layers , 1999, Nature.

[112]  L. Parajuli,et al.  Heterosynaptic structural plasticity on local dendritic segments of hippocampal CA1 neurons. , 2015, Cell reports.

[113]  A. Rodríguez-Contreras,et al.  Learning Drives Differential Clustering of Axodendritic Contacts in the Barn Owl Auditory System , 2008, The Journal of Neuroscience.

[114]  Günther Palm,et al.  Information capacity in recurrent McCulloch-Pitts networks with sparsely coded memory states , 1992 .

[115]  Edmund T Rolls,et al.  An attractor network in the hippocampus: theory and neurophysiology. , 2007, Learning & memory.

[116]  S. Sajikumar,et al.  Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD , 2004, Neurobiology of Learning and Memory.

[117]  M. W. Brown,et al.  Differential neuronal encoding of novelty, familiarity and recency in regions of the anterior temporal lobe , 1998, Neuropharmacology.

[118]  Bartlett W. Mel,et al.  Encoding and Decoding Bursts by NMDA Spikes in Basal Dendrites of Layer 5 Pyramidal Neurons , 2009, The Journal of Neuroscience.

[119]  M. Larkum,et al.  NMDA spikes enhance action potential generation during sensory input , 2014, Nature Neuroscience.

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

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