Sparse Distributed Representation of Odors in a Large-scale Olfactory Bulb Circuit

In the olfactory bulb, lateral inhibition mediated by granule cells has been suggested to modulate the timing of mitral cell firing, thereby shaping the representation of input odorants. Current experimental techniques, however, do not enable a clear study of how the mitral-granule cell network sculpts odor inputs to represent odor information spatially and temporally. To address this critical step in the neural basis of odor recognition, we built a biophysical network model of mitral and granule cells, corresponding to 1/100th of the real system in the rat, and used direct experimental imaging data of glomeruli activated by various odors. The model allows the systematic investigation and generation of testable hypotheses of the functional mechanisms underlying odor representation in the olfactory bulb circuit. Specifically, we demonstrate that lateral inhibition emerges within the olfactory bulb network through recurrent dendrodendritic synapses when constrained by a range of balanced excitatory and inhibitory conductances. We find that the spatio-temporal dynamics of lateral inhibition plays a critical role in building the glomerular-related cell clusters observed in experiments, through the modulation of synaptic weights during odor training. Lateral inhibition also mediates the development of sparse and synchronized spiking patterns of mitral cells related to odor inputs within the network, with the frequency of these synchronized spiking patterns also modulated by the sniff cycle.

[1]  T. Komiyama,et al.  Dynamic Sensory Representations in the Olfactory Bulb: Modulation by Wakefulness and Experience , 2012, Neuron.

[2]  W. Lu,et al.  Regulation of Spike Timing-Dependent Plasticity of Olfactory Inputs in Mitral Cells in the Rat Olfactory Bulb , 2012, PloS one.

[3]  Alan Carleton,et al.  Dense representation of natural odorants in the mouse olfactory bulb , 2012, Nature Neuroscience.

[4]  Hermann Riecke,et al.  Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb , 2012, PLoS Comput. Biol..

[5]  Michael L. Hines,et al.  Mitral cell spike synchrony modulated by dendrodendritic synapse location , 2012, Front. Comput. Neurosci..

[6]  Alan Carleton,et al.  Encoding Odorant Identity by Spiking Packets of Rate-Invariant Neurons in Awake Mice , 2012, PloS one.

[7]  Fan Wang,et al.  Activity-Induced Remodeling of Olfactory Bulb Microcircuits Revealed by Monosynaptic Tracing , 2011, PloS one.

[8]  Matthew C Smear,et al.  Perception of sniff phase in mouse olfaction , 2011, Nature.

[9]  A. Koulakov,et al.  Sparse Incomplete Representations: A Potential Role of Olfactory Granule Cells , 2011, Neuron.

[10]  Matthew C Smear,et al.  Precise olfactory responses tile the sniff cycle , 2011, Nature Neuroscience.

[11]  M. Wachowiak,et al.  Effect of Sniffing on the Temporal Structure of Mitral/Tufted Cell Output from the Olfactory Bulb , 2011, The Journal of Neuroscience.

[12]  Brent Doiron,et al.  Timescale-dependent shaping of correlation by olfactory bulb lateral inhibition , 2011, Proceedings of the National Academy of Sciences.

[13]  Matthew E. Phillips,et al.  Lateral Connectivity in the Olfactory Bulb is Sparse and Segregated , 2011, Front. Neural Circuits..

[14]  Upinder S Bhalla,et al.  Non-redundant odor coding by sister mitral cells revealed by light addressable glomeruli in the mouse , 2010, Nature Neuroscience.

[15]  Fred Wolf,et al.  Olfactory Coding with Patterns of Response Latencies , 2010, Neuron.

[16]  Michael L. Hines,et al.  Functional Roles of Distributed Synaptic Clusters in the Mitral–Granule Cell Network of the Olfactory Bulb , 2010, Front. Integr. Neurosci..

[17]  L. Abbott,et al.  Generating sparse and selective third-order responses in the olfactory system of the fly , 2010, Proceedings of the National Academy of Sciences.

[18]  Shawn R. Olsen,et al.  Divisive Normalization in Olfactory Population Codes , 2010, Neuron.

[19]  Jie Tan,et al.  Odor Information Processing by the Olfactory Bulb Analyzed in Gene-Targeted Mice , 2010, Neuron.

[20]  Thomas A. Cleland,et al.  Glomerular microcircuits in the olfactory bulb , 2009, Neural Networks.

[21]  Y. Kawaguchi,et al.  Cortical Inhibitory Cell Types Differentially Form Intralaminar and Interlaminar Subnetworks withExcitatory Neurons , 2009, The Journal of Neuroscience.

[22]  C. Bardy,et al.  Adult neurogenesis promotes synaptic plasticity in the olfactory bulb , 2009, Nature Neuroscience.

[23]  B. Strowbridge,et al.  Long-term plasticity of excitatory inputs to granule cells in the rat olfactory bulb , 2009, Nature Neuroscience.

[24]  C. Linster,et al.  Odor perception and olfactory bulb plasticity in adult mammals. , 2009, Journal of Neurophysiology.

[25]  Antoniu L. Fantana,et al.  Rat Olfactory Bulb Mitral Cells Receive Sparse Glomerular Inputs , 2008, Neuron.

[26]  Vikrant Kapoor,et al.  Activity-dependent gating of lateral inhibition in the mouse olfactory bulb , 2008, Nature Neuroscience.

[27]  Thomas A. Cleland,et al.  Lateral dendritic shunt inhibition can regularize mitral cell spike patterning , 2008, Journal of Computational Neuroscience.

[28]  Gordon M. Shepherd,et al.  Dendritic action potentials connect distributed dendrodendritic microcircuits , 2008, Journal of Computational Neuroscience.

[29]  Gordon M. Shepherd,et al.  Learning Mechanism for Column Formation in the Olfactory Bulb , 2007, Frontiers in integrative neuroscience.

[30]  Wei R. Chen,et al.  The olfactory granule cell: From classical enigma to central role in olfactory processing , 2007, Brain Research Reviews.

[31]  Gordon M Shepherd,et al.  An Energy Budget for the Olfactory Glomerulus , 2007, The Journal of Neuroscience.

[32]  G. Laurent,et al.  Adaptive regulation of sparseness by feedforward inhibition , 2007, Nature Neuroscience.

[33]  Adam Kepecs,et al.  Rapid and precise control of sniffing during olfactory discrimination in rats. , 2007, Journal of neurophysiology.

[34]  Vikrant Kapoor,et al.  Glomerulus-Specific, Long-Latency Activity in the Olfactory Bulb Granule Cell Network , 2006, The Journal of Neuroscience.

[35]  Gordon M Shepherd,et al.  Viral tracing identifies distributed columnar organization in the olfactory bulb , 2006, Proceedings of the National Academy of Sciences.

[36]  Veronica Egger,et al.  Dynamic connectivity in the mitral cell-granule cell microcircuit. , 2006, Seminars in cell & developmental biology.

[37]  A. Reyes,et al.  Synaptic mechanisms underlying auditory processing , 2006, Current Opinion in Neurobiology.

[38]  Kei M. Igarashi,et al.  Maps of odorant molecular features in the Mammalian olfactory bulb. , 2006, Physiological reviews.

[39]  Jamie D Boyd,et al.  Branch-Specific Ca2+ Influx from Na+-Dependent Dendritic Spikes in Olfactory Granule Cells , 2006, The Journal of Neuroscience.

[40]  Jens Midtgaard,et al.  Dendritic sodium spikelets and low-threshold calcium spikes in turtle olfactory bulb granule cells. , 2005, Journal of neurophysiology.

[41]  Michael L. Hines,et al.  The Role of Distal Dendritic Gap Junctions in Synchronization of Mitral Cell Axonal Output , 2005, Journal of Computational Neuroscience.

[42]  Processing of odor information in the olfactory bulb and cerebral lobes. , 2005, Chemical senses.

[43]  Michele Migliore,et al.  Role of an A-Type K+ Conductance in the Back-Propagation of Action Potentials in the Dendrites of Hippocampal Pyramidal Neurons , 1999, Journal of Computational Neuroscience.

[44]  Fahmeed Hyder,et al.  Odor maps of aldehydes and esters revealed by functional MRI in the glomerular layer of the mouse olfactory bulb , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Jianfeng Feng,et al.  Dendrodendritic inhibition and simulated odor responses in a detailed olfactory bulb network model. , 2003, Journal of neurophysiology.

[46]  K. Svoboda,et al.  Mechanisms of Lateral Inhibition in the Olfactory Bulb: Efficiency and Modulation of Spike-Evoked Calcium Influx into Granule Cells , 2003, The Journal of Neuroscience.

[47]  E. Audinat,et al.  Action Potential Propagation in Dendrites of Rat Mitral Cells In Vivo , 2003, The Journal of Neuroscience.

[48]  Jianhua Cang,et al.  In Vivo Whole-Cell Recording of Odor-Evoked Synaptic Transmission in the Rat Olfactory Bulb , 2003, The Journal of Neuroscience.

[49]  Gordon M Shepherd,et al.  Multiple modes of action potential initiation and propagation in mitral cell primary dendrite. , 2002, Journal of neurophysiology.

[50]  G. Lowe Inhibition of backpropagating action potentials in mitral cell secondary dendrites. , 2002, Journal of neurophysiology.

[51]  Wei R. Chen,et al.  Dynamic Gating of Spike Propagation in the Mitral Cell Lateral Dendrites , 2002, Neuron.

[52]  J. Isaacson,et al.  Mechanisms governing dendritic gamma-aminobutyric acid (GABA) release in the rat olfactory bulb. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[53]  B Sakmann,et al.  Action potential propagation in mitral cell lateral dendrites is decremental and controls recurrent and lateral inhibition in the mammalian olfactory bulb. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[54]  G. Westbrook,et al.  Tufted cell dendrodendritic inhibition in the olfactory bulb is dependent on NMDA receptor activity. , 2001, Journal of neurophysiology.

[55]  G. Westbrook,et al.  Regulation of synaptic timing in the olfactory bulb by an A-type potassium current , 1999, Nature Neuroscience.

[56]  K. Mori,et al.  The olfactory bulb: coding and processing of odor molecule information. , 1999, Science.

[57]  G M Shepherd,et al.  Synaptic organization and neurotransmitters in the rat accessory olfactory bulb. , 1999, Journal of neurophysiology.

[58]  M Ennis,et al.  Glutamate and Synaptic Plasticity at Mammalian Primary Olfactory Synapses a , 1998, Annals of the New York Academy of Sciences.

[59]  G. Westbrook,et al.  Dendrodendritic Inhibition in the Olfactory Bulb Is Driven by NMDA Receptors , 1998, The Journal of Neuroscience.

[60]  R Gervais,et al.  A re-estimation of the number of glomeruli and mitral cells in the olfactory bulb of rabbit , 1998, Brain Research.

[61]  J Bischofberger,et al.  Action potential propagation into the presynaptic dendrites of rat mitral cells , 1997, The Journal of physiology.

[62]  Nicholas T. Carnevale,et al.  The NEURON Simulation Environment , 1997, Neural Computation.

[63]  D. Wilson,et al.  NMDA-Receptor modulation of lateral inhibition and c-fos expression in olfactory bulb , 1996, Brain Research.

[64]  J. McKenzie,et al.  Whole‐cell K+ currents in identified olfactory bulb output neurones of rats. , 1996, The Journal of physiology.

[65]  P. Stanton,et al.  LTD, LTP, and the sliding threshold for long‐term synaptic plasticity , 1996, Hippocampus.

[66]  S. Nakanishi,et al.  Refinement of odor molecule tuning by dendrodendritic synaptic inhibition in the olfactory bulb. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[67]  J S Kauer,et al.  GABAergic and glutamatergic synaptic input to identified granule cells in salamander olfactory bulb. , 1994, The Journal of physiology.

[68]  S. Hyakin,et al.  Neural Networks: A Comprehensive Foundation , 1994 .

[69]  Terrence J. Sejnowski,et al.  An Efficient Method for Computing Synaptic Conductances Based on a Kinetic Model of Receptor Binding , 1994, Neural Computation.

[70]  C. Gall,et al.  Odor-induced increases in c-fos mRNA expression reveal an anatomical "unit" for odor processing in olfactory bulb. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[71]  D. K. Patneau,et al.  Functional correlates of selective long-term potentiation in the olfactory cortex and olfactory bulb , 1992, Brain Research.

[72]  C. Stevens,et al.  Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[73]  CE Jahr,et al.  A quantitative description of NMDA receptor-channel kinetic behavior , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[74]  Gordon M. Shepherd,et al.  The Olfactory Bulb , 1988 .

[75]  P B Brown,et al.  Two-point discriminability: relation to properties of the somatosensory system. , 1984, Somatosensory research.

[76]  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.

[77]  G M Shepherd,et al.  Analysis of a long‐duration inhibitory potential in mitral cells in the isolated turtle olfactory bulb. , 1981, The Journal of physiology.

[78]  G. Shepherd,et al.  Functional organization of rat olfactory bulb analysed by the 2‐deoxyglucose method , 1979, The Journal of comparative neurology.

[79]  G. Shepherd The Synaptic Organization of the Brain , 1979 .

[80]  W. Precht The synaptic organization of the brain G.M. Shepherd, Oxford University Press (1975). 364 pp., £3.80 (paperback) , 1976, Neuroscience.

[81]  A. Pinching Synaptic connexions in the glomerular layer of the olfactory bulb. , 1970, The Journal of physiology.

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

[83]  C. G. Phillips,et al.  Responses of mitral cells to stimulation of the lateral olfactory tract in the rabbit , 1963, The Journal of physiology.

[84]  H. K. Hartline,et al.  INHIBITION IN THE EYE OF LIMULUS , 1956, The Journal of general physiology.

[85]  S. W. Kuffler Discharge patterns and functional organization of mammalian retina. , 1953, Journal of neurophysiology.