Embedded ensemble encoding hypothesis: The role of the “Prepared” cell

We here reconsider current theories of neural ensembles in the context of recent discoveries about neuronal dendritic physiology. The key physiological observation is that the dendritic plateau potential produces sustained depolarization of the cell body (amplitude 10–20 mV, duration 200–500 ms). Our central hypothesis is that synaptically‐evoked dendritic plateau potentials lead to a prepared state of a neuron that favors spike generation. The plateau both depolarizes the cell toward spike threshold, and provides faster response to inputs through a shortened membrane time constant. As a result, the speed of synaptic‐to‐action potential (AP) transfer is faster during the plateau phase. Our hypothesis relates the changes from “resting” to “depolarized” neuronal state to changes in ensemble dynamics and in network information flow. The plateau provides the Prepared state (sustained depolarization of the cell body) with a time window of 200–500 ms. During this time, a neuron can tune into ongoing network activity and synchronize spiking with other neurons to provide a coordinated Active state (robust firing of somatic APs), which would permit “binding” of signals through coordination of neural activity across a population. The transient Active ensemble of neurons is embedded in the longer‐lasting Prepared ensemble of neurons. We hypothesize that “embedded ensemble encoding” may be an important organizing principle in networks of neurons.

[1]  W. DeBello,et al.  Input clustering in the normal and learned circuits of adult barn owls , 2015, Neurobiology of Learning and Memory.

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

[3]  Zizhen Zhang,et al.  Norepinephrine Drives Persistent Activity in Prefrontal Cortex via Synergistic α1 and α2 Adrenoceptors , 2013, PloS one.

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

[5]  T. Poggio,et al.  Nonlinear interactions in a dendritic tree: localization, timing, and role in information processing. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S. Dura-Bernal,et al.  Top-Down Feedback in an HMAX-Like Cortical Model of Object Perception Based on Hierarchical Bayesian Networks and Belief Propagation , 2012, PloS one.

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

[8]  Idan Segev,et al.  Ion Channel Stochasticity May Be Critical in Determining the Reliability and Precision of Spike Timing , 1998, Neural Computation.

[9]  P. Detwiler,et al.  Directionally selective calcium signals in dendrites of starburst amacrine cells , 2002, Nature.

[10]  Da-Ting Lin,et al.  Visualization of NMDA receptor-dependent AMPA receptor synaptic plasticity in vivo , 2015, Nature Neuroscience.

[11]  Joshua L. Plotkin,et al.  Synaptically driven state transitions in distal dendrites of striatal spiny neurons , 2011, Nature Neuroscience.

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

[13]  P. Goldman-Rakic Cellular basis of working memory , 1995, Neuron.

[14]  B. Baars The conscious access hypothesis: origins and recent evidence , 2002, Trends in Cognitive Sciences.

[15]  B. Kampa,et al.  Synaptic integration in dendritic trees. , 2005, Journal of neurobiology.

[16]  W. Bair Spike timing in the mammalian visual system , 1999, Current Opinion in Neurobiology.

[17]  P. Goldman-Rakic,et al.  Burst generation in rat pyramidal neurones by regenerative potentials elicited in a restricted part of the basilar dendritic tree , 2004, The Journal of physiology.

[18]  A. Holtmaat,et al.  Sensory-evoked LTP driven by dendritic plateau potentials in vivo , 2014, Nature.

[19]  Sean A. Spence,et al.  Descartes' Error: Emotion, Reason and the Human Brain , 1995 .

[20]  Andrea Hasenstaub,et al.  Persistent cortical activity: mechanisms of generation and effects on neuronal excitability. , 2003, Cerebral cortex.

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

[22]  R. Llinás,et al.  Consciousness and the Brain , 2001 .

[23]  W. Gan,et al.  Branch-specific dendritic Ca2+ spikes cause persistent synaptic plasticity , 2015, Nature.

[24]  Karl J. Friston Hierarchical Models in the Brain , 2008, PLoS Comput. Biol..

[25]  J. Schiller,et al.  NMDA spikes in basal dendrites of cortical pyramidal neurons , 2000, Nature.

[26]  F. Crick Function of the thalamic reticular complex: the searchlight hypothesis. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. Desimone,et al.  Stimulus-selective properties of inferior temporal neurons in the macaque , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[28]  W Singer,et al.  Visual feature integration and the temporal correlation hypothesis. , 1995, Annual review of neuroscience.

[29]  Nathalie L Rochefort,et al.  Reactivation of the same synapses during spontaneous up states and sensory stimuli. , 2013, Cell reports.

[30]  R. Yuste,et al.  Input Summation by Cultured Pyramidal Neurons Is Linear and Position-Independent , 1998, The Journal of Neuroscience.

[31]  J. Fellous,et al.  A role for NMDA-receptor channels in working memory , 1998, Nature Neuroscience.

[32]  Hiroyoshi Miyakawa,et al.  A plateau potential mediated by the activation of extrasynaptic NMDA receptors in rat hippocampal CA1 pyramidal neurons , 2008, The European journal of neuroscience.

[33]  J. Rosenkranz,et al.  Effects of Repeated Stress on Excitatory Drive of Basal Amygdala Neurons In Vivo , 2013, Neuropsychopharmacology.

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

[35]  Claudia Clopath,et al.  Modeling somatic and dendritic spike mediated plasticity at the single neuron and network level , 2017, Nature Communications.

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

[37]  J. Lisman,et al.  The Hippocampal-VTA Loop: Controlling the Entry of Information into Long-Term Memory , 2005, Neuron.

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

[39]  J. Rinzel,et al.  The role of dendrites in auditory coincidence detection , 1998, Nature.

[40]  G. Elston Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function. , 2003, Cerebral cortex.

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

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

[43]  M. Larkum A cellular mechanism for cortical associations: an organizing principle for the cerebral cortex , 2013, Trends in Neurosciences.

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

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

[46]  William E. Allen,et al.  Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex , 2017, Neuron.

[47]  H Eichenbaum,et al.  Thinking about brain cell assemblies. , 1993, Science.

[48]  C. Koch,et al.  The Neural Correlates of Consciousness , 2008, Annals of the New York Academy of Sciences.

[49]  L. Cauller Layer I of primary sensory neocortex: where top-down converges upon bottom-up , 1995, Behavioural Brain Research.

[50]  Peter Dayan,et al.  Networks, circuits and computation , 2011, Current Opinion in Neurobiology.

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

[52]  B. Nolan Boosting slow oscillations during sleep potentiates memory , 2008 .

[53]  P. Goldman-Rakic,et al.  Temporally irregular mnemonic persistent activity in prefrontal neurons of monkeys during a delayed response task. , 2003, Journal of neurophysiology.

[54]  P. Frankland,et al.  Finding the engram , 2015, Nature Reviews Neuroscience.

[55]  A. Larkman,et al.  Dendritic morphology of pyramidal neurones of the visual cortex of the rat: III. Spine distributions , 1991, The Journal of comparative neurology.

[56]  L. Barrett‐Lennard,et al.  Graded persistent activity in entorhinal cortex neurons , 2002 .

[57]  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.

[58]  Yi Zhou,et al.  Functional dissection of synaptic circuits: in vivo patch-clamp recording in neuroscience , 2015, Front. Neural Circuits.

[59]  B. Sakmann,et al.  ‐Dynamic representation of whisker deflection by synaptic potentials in spiny stellate and pyramidal cells in the barrels and septa of layer 4 rat somatosensory cortex , 2002, The Journal of physiology.

[60]  T. Sejnowski,et al.  Neurocomputational models of working memory , 2000, Nature Neuroscience.

[61]  Christof Koch,et al.  The role of single neurons in information processing , 2000, Nature Neuroscience.

[62]  S. Antic,et al.  Extrasynaptic Glutamate Receptor Activation as Cellular Bases for Dynamic Range Compression in Pyramidal Neurons , 2012, Front. Physio..

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

[64]  Idan Segev,et al.  The information efficacy of a synapse , 2002, Nature Neuroscience.

[65]  W. Singer,et al.  Correlation analysis of corticotectal interactions in the cat visual system. , 1998, Journal of neurophysiology.

[66]  R. Llinás,et al.  Consciousness and the brain. The thalamocortical dialogue in health and disease. , 2001, Annals of the New York Academy of Sciences.

[67]  J B Poline,et al.  Cerebral mechanisms of word masking and unconscious repetition priming , 2001, Nature Neuroscience.

[68]  Pablo E. Jercog,et al.  Neural ensemble dynamics underlying a long-term associative memory , 2017, Nature.

[69]  Matthew E. Larkum,et al.  Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents , 2017, Nature Communications.

[70]  N. Wittenburg,et al.  Transformation from temporal to rate coding in a somatosensory thalamocortical pathway , 2022 .

[71]  Earl K. Miller,et al.  On memories, neural ensembles and mental flexibility , 2017, NeuroImage.

[72]  M. Steriade,et al.  Natural waking and sleep states: a view from inside neocortical neurons. , 2001, Journal of neurophysiology.

[73]  Michèle Fabre-Thorpe,et al.  At 120 msec You Can Spot the Animal but You Don't Yet Know It's a Dog , 2015, Journal of Cognitive Neuroscience.

[74]  W. Singer,et al.  Dynamic predictions: Oscillations and synchrony in top–down processing , 2001, Nature Reviews Neuroscience.

[75]  Annabelle C Singer,et al.  Illuminating Neural Circuits: From Molecules to MRI , 2017, The Journal of Neuroscience.

[76]  Thomas J. McBride,et al.  Input clustering and the microscale structure of local circuits , 2014, Front. Neural Circuits.

[77]  Kevin L. Briggman,et al.  Wiring specificity in the direction-selectivity circuit of the retina , 2011, Nature.

[78]  V. Mountcastle The columnar organization of the neocortex. , 1997, Brain : a journal of neurology.

[79]  G. Edelman,et al.  Reentry and the problem of integrating multiple cortical areas: simulation of dynamic integration in the visual system. , 1992, Cerebral cortex.

[80]  Functional Integration of Large-Scale Brain Networks , 2013, The Journal of Neuroscience.

[81]  B L McNaughton,et al.  Dynamics of the hippocampal ensemble code for space. , 1993, Science.

[82]  Srdjan D Antic,et al.  Voltage and calcium transients in basal dendrites of the rat prefrontal cortex , 2007, The Journal of physiology.

[83]  T. Wiesel,et al.  Clustered intrinsic connections in cat visual cortex , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[85]  D. McCormick,et al.  Synaptic Mechanisms of Tight Spike Synchrony at Gamma Frequency in Cerebral Cortex , 2015, The Journal of Neuroscience.

[86]  T. L. Watson,et al.  A Bayesian approach to person perception , 2015, Consciousness and Cognition.

[87]  Boris S. Gutkin,et al.  Contribution of sublinear and supralinear dendritic integration to neuronal computations , 2015, Front. Cell. Neurosci..

[88]  Dylan R. Muir,et al.  Specific excitatory connectivity for feature integration in mouse primary visual cortex , 2017, bioRxiv.

[89]  M. Hasselmo,et al.  Graded persistent activity in entorhinal cortex neurons , 2002, Nature.

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

[91]  William W. Lytton,et al.  Emergence of Physiological Oscillation Frequencies in a Computer Model of Neocortex , 2011, Front. Comput. Neurosci..

[92]  Adam G. Carter,et al.  Glutamate Spillover Promotes the Generation of NMDA Spikes , 2011, The Journal of Neuroscience.

[93]  A. Polsky,et al.  Submillisecond Precision of the Input-Output Transformation Function Mediated by Fast Sodium Dendritic Spikes in Basal Dendrites of CA1 Pyramidal Neurons , 2003, The Journal of Neuroscience.

[94]  S. Zeki,et al.  The functional organization of area V2, I: Specialization across stripes and layers , 2002, Visual Neuroscience.

[95]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[96]  Daniel N Hill,et al.  Multibranch activity in basal and tuft dendrites during firing of layer 5 cortical neurons in vivo , 2013, Proceedings of the National Academy of Sciences.

[97]  Kevin S. Brown,et al.  Cooperation between the default mode network and the frontal–parietal network in the production of an internal train of thought , 2012, Brain Research.

[98]  Charles J. Wilson,et al.  The origins of two-state spontaneous membrane potential fluctuations of neostriatal spiny neurons , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[99]  W Rall,et al.  Matching dendritic neuron models to experimental data. , 1992, Physiological reviews.

[100]  T. Sejnowski,et al.  Correlated neuronal activity and the flow of neural information , 2001, Nature Reviews Neuroscience.

[101]  J. Magee,et al.  On the Initiation and Propagation of Dendritic Spikes in CA1 Pyramidal Neurons , 2004, The Journal of Neuroscience.

[102]  E. John,et al.  Invariant Reversible QEEG Effects of Anesthetics , 2001, Consciousness and Cognition.

[103]  B. Harrison,et al.  Influence of the fusiform gyrus on amygdala response to emotional faces in the non-clinical range of social anxiety , 2009, Psychological Medicine.

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

[105]  S. Antic,et al.  Spiny neurons of amygdala, striatum, and cortex use dendritic plateau potentials to detect network UP states , 2014, Front. Cell. Neurosci..

[106]  Roger D. Traub,et al.  Rates and Rhythms: A Synergistic View of Frequency and Temporal Coding in Neuronal Networks , 2012, Neuron.

[107]  Tiago Branco,et al.  Active dendritic integration as a mechanism for robust and precise grid cell firing , 2017, Nature Neuroscience.

[108]  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.

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

[110]  György Buzsáki,et al.  High frequency oscillations in the intact brain , 2012, Progress in Neurobiology.

[111]  E. Fransén,et al.  Long‐lasting small‐amplitude TRP‐mediated dendritic depolarizations in CA1 pyramidal neurons are intrinsically stable and originate from distal tuft regions , 2012, The European journal of neuroscience.

[112]  A. Grinvald,et al.  Interaction of sensory responses with spontaneous depolarization in layer 2/3 barrel cortex , 2003, Proceedings of the National Academy of Sciences of the United States of America.

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

[114]  W. Singer,et al.  Temporal binding and the neural correlates of sensory awareness , 2001, Trends in Cognitive Sciences.

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

[116]  Christof Koch,et al.  Spike-timing control by dendritic plateau potentials in the presence of synaptic barrages , 2014, Front. Comput. Neurosci..

[117]  Bruno A Olshausen,et al.  Sparse coding of sensory inputs , 2004, Current Opinion in Neurobiology.

[118]  Huxley Af,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve. 1952. , 1990 .

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

[120]  Rodrigo M. Braga,et al.  Echoes of the Brain within Default Mode, Association, and Heteromodal Cortices , 2013, The Journal of Neuroscience.

[121]  Haim Sompolinsky,et al.  Computational neuroscience: beyond the local circuit , 2014, Current Opinion in Neurobiology.

[122]  Tiago Branco,et al.  Dendritic nonlinearities are tuned for efficient spike-based computations in cortical circuits , 2015, eLife.

[123]  Jonas Persson,et al.  Brain systems underlying attentional control and emotional distraction during working memory encoding , 2014, NeuroImage.

[124]  W. Singer,et al.  The gamma cycle , 2007, Trends in Neurosciences.

[125]  Charles J. Wilson,et al.  Up and down states , 2008, Scholarpedia.

[126]  L. Abbott,et al.  Neural network dynamics. , 2005, Annual review of neuroscience.

[127]  Bartlett W. Mel Synaptic integration in an excitable dendritic tree. , 1993, Journal of neurophysiology.

[128]  Maxim Volgushev,et al.  Precise Long-Range Synchronization of Activity and Silence in Neocortical Neurons during Slow-Wave Sleep , 2006, The Journal of Neuroscience.

[129]  V. Lamme,et al.  The distinct modes of vision offered by feedforward and recurrent processing , 2000, Trends in Neurosciences.

[130]  T. Wiesel,et al.  Functional organization of the visual cortex. , 1983, Progress in brain research.

[131]  David Ferster,et al.  Membrane Potential Synchrony in Primary Visual Cortex during Sensory Stimulation , 2010, Neuron.

[132]  D. Baranes,et al.  Dendritic Branch Intersections Are Structurally Regulated Targets for Efficient Axonal Wiring and Synaptic Clustering , 2013, PloS one.

[133]  J. Magee Observations on Clustered Synaptic Plasticity and Highly Structured Input Patterns , 2011, Neuron.

[134]  M. Häusser,et al.  Synaptic Integration Gradients in Single Cortical Pyramidal Cell Dendrites , 2011, Neuron.

[135]  James G. King,et al.  Reconstruction and Simulation of Neocortical Microcircuitry , 2015, Cell.

[136]  B. Ermentrout,et al.  Chemical and electrical synapses perform complementary roles in the synchronization of interneuronal networks. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[137]  O. Paulsen,et al.  Cortical Up states induce the selective weakening of subthreshold synaptic inputs , 2017, Nature Communications.

[138]  S. Antic,et al.  Initiation of Sodium Spikelets in Basal Dendrites of Neocortical Pyramidal Neurons , 2005, The Journal of Membrane Biology.

[139]  Adam Bleckert,et al.  A Role for Synaptic Input Distribution in a Dendritic Computation of Motion Direction in the Retina , 2016, Neuron.

[140]  R. Silver,et al.  Synaptic connections between layer 4 spiny neurone‐ layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column , 2002, The Journal of physiology.

[141]  Tony Ro,et al.  Feedback Contributions to Visual Awareness in Human Occipital Cortex , 2003, Current Biology.

[142]  D. Perrett,et al.  Visual neurones responsive to faces in the monkey temporal cortex , 2004, Experimental Brain Research.

[143]  Srdjan D Antic,et al.  Voltage imaging to understand connections and functions of neuronal circuits. , 2016, Journal of neurophysiology.

[144]  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.

[145]  Michael J. Berry,et al.  Predictive information in a sensory population , 2013, Proceedings of the National Academy of Sciences.

[146]  G. Shepherd,et al.  Theoretical reconstruction of field potentials and dendrodendritic synaptic interactions in olfactory bulb. , 1968, Journal of neurophysiology.

[147]  Karl Deisseroth,et al.  Closed-Loop and Activity-Guided Optogenetic Control , 2015, Neuron.

[148]  Wolf Singer,et al.  Neuronal Synchrony: A Versatile Code for the Definition of Relations? , 1999, Neuron.

[149]  Huaixing Wang,et al.  A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex , 2008, Proceedings of the National Academy of Sciences.