Stimulus dependent diversity and stereotypy in the output of an olfactory functional unit

Olfactory inputs are organized in an array of functional units (glomeruli), each relaying information from sensory neurons expressing a given odorant receptor to a small population of output neurons, mitral/tufted (MT) cells. MT cells respond heterogeneously to odorants, and how the responses encode stimulus features is unknown. We recorded in awake mice responses from “sister” MT cells that receive input from a functionally characterized, genetically identified glomerulus, corresponding to a specific receptor (M72). Despite receiving similar inputs, sister MT cells exhibit temporally diverse, concentration-dependent, excitatory and inhibitory responses to most M72 ligands. In contrast, the strongest known ligand for M72 elicits temporally stereotyped, early excitatory responses in sister MT cells, consistent across a range of concentrations. Our data suggest that information about ligand affinity is encoded in the collective stereotypy or diversity of activity among sister MT cells within a glomerular functional unit in a concentration-tolerant manner.Mitral/tufted (MT) cells connect to a single glomerulus and receive inputs from sensory neurons expressing the same odorant receptor. Here the authors report that sister MT cells connected to the M72 glomerulus exhibit variable responses to most M72 ligands but respond in a reproducible and stereotyped way to a high-affinity M72 ligand.

[1]  Troy W. Margrie,et al.  A biophysical signature of network affiliation and sensory processing in mitral cells , 2012, Nature.

[2]  Uri T Eden,et al.  A point process framework for relating neural spiking activity to spiking history, neural ensemble, and extrinsic covariate effects. , 2005, Journal of neurophysiology.

[3]  Bert Sakmann,et al.  Reciprocal intraglomerular excitation and intra‐ and interglomerular lateral inhibition between mouse olfactory bulb mitral cells , 2002, The Journal of physiology.

[4]  Joshua T. Dudman,et al.  RIVETS: A Mechanical System for In Vivo and In Vitro Electrophysiology and Imaging , 2014, PloS one.

[5]  T. Komiyama,et al.  Parvalbumin-Expressing Interneurons Linearly Control Olfactory Bulb Output , 2013, Neuron.

[6]  Minmin Luo,et al.  Response Correlation Maps of Neurons in the Mammalian Olfactory Bulb , 2001, Neuron.

[7]  Eero P. Simoncelli,et al.  Spatio-temporal correlations and visual signalling in a complete neuronal population , 2008, Nature.

[8]  Alan Gelperin,et al.  Sparse Odor Coding in Awake Behaving Mice , 2006, The Journal of Neuroscience.

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

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

[11]  N. Urban,et al.  Intrinsic biophysical diversity decorrelates neuronal firing while increasing information content , 2010, Nature Neuroscience.

[12]  Matt Wachowiak,et al.  In Vivo Imaging of Neuronal Activity by Targeted Expression of a Genetically Encoded Probe in the Mouse , 2004, Neuron.

[13]  H. Sompolinsky,et al.  Compressed sensing, sparsity, and dimensionality in neuronal information processing and data analysis. , 2012, Annual review of neuroscience.

[14]  Alexei A. Koulakov,et al.  A primacy code for odor identity , 2017, Nature Communications.

[15]  M. M. Mozell,et al.  Evidence for a Chromatographic Model of Olfaction , 1970, The Journal of general physiology.

[16]  Naoshige Uchida,et al.  Robust Odor Coding via Inhalation-Coupled Transient Activity in the Mammalian Olfactory Bulb , 2010, Neuron.

[17]  Detlev Schild,et al.  Odor coding by modules of coherent mitral/tufted cells in the vertebrate olfactory bulb , 2009, Proceedings of the National Academy of Sciences.

[18]  Kevin M Franks,et al.  Complementary codes for odor identity and intensity in olfactory cortex , 2017, eLife.

[19]  Jennifer D Whitesell,et al.  Interglomerular Lateral Inhibition Targeted on External Tufted Cells in the Olfactory Bulb , 2013, The Journal of Neuroscience.

[20]  Gordon M Shepherd,et al.  The olfactory glomerulus: A cortical module with specific functions , 2005, Journal of neurocytology.

[21]  Adam Dewan,et al.  Uncoupling stimulus specificity and glomerular position in the mouse olfactory system , 2012, Molecular and Cellular Neuroscience.

[22]  Sreekanth H. Chalasani,et al.  Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators , 2009, Nature Methods.

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

[24]  Yevgeniy B. Sirotin,et al.  Single Scale for Odor Intensity in Rat Olfaction , 2014, Current Biology.

[25]  Mijung Park,et al.  Receptive Field Inference with Localized Priors , 2011, PLoS Comput. Biol..

[26]  Tatsuya Yamasoba,et al.  Odorant Response Properties of Individual Neurons in an Olfactory Glomerular Module , 2013, Neuron.

[27]  Richard Axel,et al.  Visualizing an Olfactory Sensory Map , 1996, Cell.

[28]  L. Paninski Maximum likelihood estimation of cascade point-process neural encoding models , 2004, Network.

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

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

[31]  Ryan M Carey,et al.  Temporal structure of receptor neuron input to the olfactory bulb imaged in behaving rats. , 2009, Journal of neurophysiology.

[32]  Susana Q. Lima,et al.  PINP: A New Method of Tagging Neuronal Populations for Identification during In Vivo Electrophysiological Recording , 2009, PloS one.

[33]  Andreas T. Schaefer,et al.  Theta oscillation coupled spike latencies yield computational vigour in a mammalian sensory system , 2003, The Journal of physiology.

[34]  Steve M. Potter,et al.  Structure and Emergence of Specific Olfactory Glomeruli in the Mouse , 2001, The Journal of Neuroscience.

[35]  Philippe Litaudon,et al.  Respiratory modulation of olfactory neurons in the rodent brain. , 2006, Chemical senses.

[36]  A. Grinvald,et al.  Spatio-Temporal Dynamics of Odor Representations in the Mammalian Olfactory Bulb , 2002, Neuron.

[37]  Yevgeniy B. Sirotin,et al.  Neural Coding of Perceived Odor Intensity1,2,3 , 2015, eNeuro.

[38]  Dmitry Rinberg,et al.  Multiple perceptible signals from a single olfactory glomerulus , 2014, Nature Neuroscience.

[39]  Maneesh Sahani,et al.  Evidence Optimization Techniques for Estimating Stimulus-Response Functions , 2002, NIPS.

[40]  Heike S. Demmer,et al.  Broadly tuned and respiration-independent inhibition in the olfactory bulb of awake mice , 2014, bioRxiv.

[41]  Andreas T. Schaefer,et al.  Two Distinct Channels of Olfactory Bulb Output , 2012, Neuron.

[42]  J. Reisert,et al.  Olfactory receptor neuron responses coding for rapid odour sampling , 2011, Journal of Physiology.

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

[44]  J. Greer,et al.  Targeting genes for self-excision in the germ line. , 1999, Genes & development.

[45]  Lynn Hazan,et al.  Klusters, NeuroScope, NDManager: A free software suite for neurophysiological data processing and visualization , 2006, Journal of Neuroscience Methods.

[46]  R. Tsien,et al.  Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein , 2004, Nature Biotechnology.

[47]  Mijung Park,et al.  Bayesian inference for low rank spatiotemporal neural receptive fields , 2013, NIPS.

[48]  Peter Mombaerts,et al.  Odorant Receptor Expression Defines Functional Units in the Mouse Olfactory System , 2002, The Journal of Neuroscience.

[49]  Kai Zhao,et al.  Airflow and nanoparticle deposition in rat nose under various breathing and sniffing conditions: a computational evaluation of the unsteady effect. , 2010, Journal of aerosol science.

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

[51]  A. Holley,et al.  Convergence in the olfactory system: quantitative aspects of odour sensitivity. , 1978, Journal of theoretical biology.

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