Interglomerular Lateral Inhibition Targeted on External Tufted Cells in the Olfactory Bulb

Lateral inhibition between neurons occurs in many different sensory systems, where it can perform such functions as contrast enhancement. In the olfactory bulb, lateral inhibition may occur between odorant receptor-specific glomeruli that are linked anatomically by GABAergic granule cells (GCs) and cells within the glomerular layer, although evidence supporting lateral inhibition at a functional level is modest. Here, we used patch-clamp, imaging, and glutamate uncaging methods in rat olfactory bulb slices to test for the presence of interglomerular lateral inhibition, as well as its underlying mechanisms. We found that a conditioning stimulus applied at one or a small group of glomeruli could suppress stimulus-evoked excitation of output mitral cells (MCs) at another glomerulus for interstimulus intervals of 20–50 ms and glomerular separations of up to 600 μm. The observed lateral inhibition was entirely dependent on circuitry within the glomerular layer, rather than GCs, and it involved GABAergic synaptic inputs that were targeted mainly onto tufted cells, which act as intermediaries in the excitation between olfactory sensory neurons and MCs. The key cell type responsible for mediating lateral interactions between glomeruli were GABAergic short-axon cells. These results suggest a functional segregation of GABAergic cells within the bulb, with one set located in the glomerular layer mediating suppression of MC spiking across glomeruli, and a second set, the GCs, synchronizing different glomeruli.

[1]  T. A. Harrison,et al.  Discrimination among odorants by single neurons of the rat olfactory bulb. , 1989, Journal of neurophysiology.

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

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

[4]  David H Gire,et al.  Control of On/Off Glomerular Signaling by a Local GABAergic Microcircuit in the Olfactory Bulb , 2009, The Journal of Neuroscience.

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

[6]  Peter Mombaerts,et al.  Olfactory coding: Revealing intrinsic representations of odors , 2001, Current Biology.

[7]  S. Hentges,et al.  Expression of GABAergic and glutamatergic phenotypic markers in hypothalamic proopiomelanocortin neurons , 2012, The Journal of comparative neurology.

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

[9]  Jennifer D Whitesell,et al.  Mitral Cells in the Olfactory Bulb Are Mainly Excited through a Multistep Signaling Path , 2012, The Journal of Neuroscience.

[10]  Markus Meister,et al.  Precision and diversity in an odor map on the olfactory bulb , 2009, Nature Neuroscience.

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

[12]  J. Isaacson,et al.  Olfactory Reciprocal Synapses: Dendritic Signaling in the CNS , 1998, Neuron.

[13]  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.

[14]  L. C. Katz,et al.  Optical Imaging of Odorant Representations in the Mammalian Olfactory Bulb , 1999, Neuron.

[15]  M. T. Shipley,et al.  Centre–surround inhibition among olfactory bulb glomeruli , 2003, Nature.

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

[17]  A. Keller,et al.  Long-Lasting Depolarizations in Mitral Cells of the Rat Olfactory Bulb , 2000, The Journal of Neuroscience.

[18]  N. Schoppa,et al.  Dendritic processing within olfactory bulb circuits , 2003, Trends in Neurosciences.

[19]  Winfried Wiegraebe,et al.  Distributed representation of chemical features and tunotopic organization of glomeruli in the mouse olfactory bulb , 2012, Proceedings of the National Academy of Sciences.

[20]  M. T. Shipley,et al.  External Tufted Cells: A Major Excitatory Element That Coordinates Glomerular Activity , 2004, The Journal of Neuroscience.

[21]  D. Friedman,et al.  Both electrical and chemical synapses mediate fast network oscillations in the olfactory bulb. , 2003, Journal of neurophysiology.

[22]  Rainer W Friedrich,et al.  Temporal Dynamics and Latency Patterns of Receptor Neuron Input to the Olfactory Bulb , 2006, The Journal of Neuroscience.

[23]  Alan Carleton,et al.  Dynamic Ensemble Odor Coding in the Mammalian Olfactory Bulb: Sensory Information at Different Timescales , 2008, Neuron.

[24]  N Buonviso,et al.  Response similarity to odors in olfactory bulb output cells presumed to be connected to the same glomerulus: electrophysiological study using simultaneous single-unit recordings. , 1990, Journal of neurophysiology.

[25]  Alan Carleton,et al.  Interplay between Local GABAergic Interneurons and Relay Neurons Generates γ Oscillations in the Rat Olfactory Bulb , 2004, The Journal of Neuroscience.

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

[27]  N. Uchida,et al.  Synchronized oscillatory discharges of mitral/tufted cells with different molecular receptive ranges in the rabbit olfactory bulb. , 1999, Journal of neurophysiology.

[28]  L. Cohen,et al.  Interglomerular center-surround inhibition shapes odorant-evoked input to the mouse olfactory bulb in vivo. , 2006, Journal of neurophysiology.

[29]  John W. Scott,et al.  Sniffing and spatiotemporal coding in olfaction. , 2006, Chemical senses.

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

[31]  N. Urban,et al.  Computing with Dendrodendritic Synapses in the Olfactory Bulb , 2009, Annals of the New York Academy of Sciences.

[32]  M. T. Shipley,et al.  Intraglomerular inhibition shapes the strength and temporal structure of glomerular output. , 2012, Journal of neurophysiology.

[33]  Matthew E. Phillips,et al.  Respiration Drives Network Activity and Modulates Synaptic and Circuit Processing of Lateral Inhibition in the Olfactory Bulb , 2012, The Journal of Neuroscience.

[34]  Serge Charpak,et al.  Monosynaptic and Polysynaptic Feed-Forward Inputs to Mitral Cells from Olfactory Sensory Neurons , 2011, The Journal of Neuroscience.

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

[36]  N. Schoppa,et al.  Synchronization of Olfactory Bulb Mitral Cells by Precisely Timed Inhibitory Inputs , 2006, Neuron.

[37]  T. Powell,et al.  The neuron types of the glomerular layer of the olfactory bulb. , 1971, Journal of cell science.

[38]  Serge Charpak,et al.  External Tufted Cells Drive the Output of Olfactory Bulb Glomeruli , 2009, The Journal of Neuroscience.

[39]  Nicolas Fourcaud-Trocmé,et al.  Correlation-induced Synchronization of Oscillations in Olfactory Bulb Neurons , 2022 .

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

[41]  Matt Wachowiak,et al.  Odorant Representations Are Modulated by Intra- but Not Interglomerular Presynaptic Inhibition of Olfactory Sensory Neurons , 2005, Neuron.

[42]  Praveen Sethupathy,et al.  Non-topographical contrast enhancement in the olfactory bulb , 2006, BMC Neuroscience.

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

[44]  B. Strowbridge,et al.  Multiple Modes of Synaptic Excitation of Olfactory Bulb Granule Cells , 2007, The Journal of Neuroscience.

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

[46]  M. Wachowiak.  All in a Sniff: Olfaction as a Model for Active Sensing , 2011, Neuron.

[47]  Adam C. Puche,et al.  Inhibition of Olfactory Receptor Neuron Input to Olfactory Bulb Glomeruli Mediated by Suppression of Presynaptic Calcium Influx , 2005 .

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

[49]  Yuchio Yanagawa,et al.  Molecular Identity of Periglomerular and Short Axon Cells , 2010, The Journal of Neuroscience.

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

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

[52]  M. Frotscher,et al.  Adult generation of glutamatergic olfactory bulb interneurons , 2009, Nature Neuroscience.

[53]  E. Coddington,et al.  All-or-none population bursts temporally constrain surround inhibition between mouse olfactory glomeruli , 2010, Brain Research Bulletin.

[54]  Y. Yanagawa,et al.  Quantitative chemical composition of cortical GABAergic neurons revealed in transgenic venus-expressing rats. , 2008, Cerebral cortex.