Mitral Cells in the Olfactory Bulb Are Mainly Excited through a Multistep Signaling Path

Within the olfactory system, information flow from the periphery onto output mitral cells (MCs) of the olfactory bulb (OB) has been thought to be mediated by direct synaptic inputs from olfactory sensory neurons (OSNs). Here, we performed patch-clamp measurements in rat and mouse OB slices to investigate mechanisms of OSN signaling onto MCs, including the assumption of a direct path, using electrical and optogenetic stimulation methods that selectively activated OSNs. We found that MCs are in fact not typically activated by direct OSN inputs and instead require a multistep, diffuse mechanism involving another glutamatergic cell type, the tufted cells. The preference for a multistep mechanism reflects the fact that signals arising from direct OSN inputs are drastically shunted by connexin 36-mediated gap junctions on MCs, but not tufted cells. An OB circuit with tufted cells intermediate between OSNs and MCs suggests that considerable processing of olfactory information occurs before its reaching MCs.

[1]  M. T. Shipley,et al.  Tonic and synaptically evoked presynaptic inhibition of sensory input to the rat olfactory bulb via GABA(B) heteroreceptors. , 2000, Journal of neurophysiology.

[2]  J. Isaacson,et al.  Intraglomerular inhibition: signaling mechanisms of an olfactory microcircuit , 2005, Nature Neuroscience.

[3]  M. Feller,et al.  Mechanisms underlying spontaneous patterned activity in developing neural circuits , 2010, Nature Reviews Neuroscience.

[4]  G. Lowe,et al.  Calcium permeable AMPA receptors and autoreceptors in external tufted cells of rat olfactory bulb , 2007, Neuroscience.

[5]  T. Kosaka,et al.  Structure of intraglomerular dendritic tufts of mitral cells and their contacts with olfactory nerve terminals and calbindin‐immunoreactive type 2 periglomerular neurons , 2001, The Journal of comparative neurology.

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

[7]  Dejan Zecevic,et al.  Functional Structure of the Mitral Cell Dendritic Tuft in the Rat Olfactory Bulb , 2008, The Journal of Neuroscience.

[8]  G. Westbrook,et al.  Glomerulus-Specific Synchronization of Mitral Cells in the Olfactory Bulb , 2001, Neuron.

[9]  T. Margrie,et al.  Glutamatergic transmission and plasticity between olfactory bulb mitral cells , 2008, The Journal of physiology.

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

[11]  M. T. Shipley,et al.  Olfactory Bulb Glomeruli: External Tufted Cells Intrinsically Burst at Theta Frequency and Are Entrained by Patterned Olfactory Input , 2004, The Journal of Neuroscience.

[12]  B. Connors,et al.  Stability of Electrical Coupling despite Massive Developmental Changes of Intrinsic Neuronal Physiology , 2009, The Journal of Neuroscience.

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

[14]  M. T. Shipley,et al.  Dopamine D2 receptor-mediated presynaptic inhibition of olfactory nerve terminals. , 2001, Journal of neurophysiology.

[15]  B. Connors,et al.  Synchronous Activity of Inhibitory Networks in Neocortex Requires Electrical Synapses Containing Connexin36 , 2001, Neuron.

[16]  N. Spruston,et al.  Determinants of Voltage Attenuation in Neocortical Pyramidal Neuron Dendrites , 1998, The Journal of Neuroscience.

[17]  Michael T Shipley,et al.  Multiple Conductances Cooperatively Regulate Spontaneous Bursting in Mouse Olfactory Bulb External Tufted Cells , 2008, The Journal of Neuroscience.

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

[19]  Jason B. Castro,et al.  Subthreshold Glutamate Release from Mitral Cell Dendrites , 2009, The Journal of Neuroscience.

[20]  C. Greer,et al.  Compartmental organization of the olfactory bulb glomerulus , 1999, The Journal of comparative neurology.

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

[22]  G. Westbrook,et al.  Experience-dependent maturation of the glomerular microcircuit , 2009, Proceedings of the National Academy of Sciences.

[23]  G. Westbrook,et al.  AMPA autoreceptors drive correlated spiking in olfactory bulb glomeruli , 2002, Nature Neuroscience.

[24]  M. T. Shipley,et al.  Evidence for GABAB-mediated inhibition of transmission from the olfactory nerve to mitral cells in the rat olfactory bulb , 1994, Brain Research Bulletin.

[25]  C. Koch,et al.  Recurrent excitation in neocortical circuits , 1995, Science.

[26]  Zhishang Zhou,et al.  Intrabulbar Projecting External Tufted Cells Mediate a Timing-Based Mechanism That Dynamically Gates Olfactory Bulb Output , 2008, The Journal of Neuroscience.

[27]  Yoshihiro Yoshihara,et al.  Mitral and tufted cells differ in the decoding manner of odor maps in the rat olfactory bulb. , 2004, Journal of neurophysiology.

[28]  Gordon M. Shepherd,et al.  The Olfactory Bulb , 1998 .

[29]  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.

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

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

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

[33]  J. W. Scott,et al.  Organization of inhibition in the rat olfactory bulb external plexiform layer. , 1993, Journal of neurophysiology.

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

[35]  G M Shepherd,et al.  Forward and backward propagation of dendritic impulses and their synaptic control in mitral cells. , 1997, Science.

[36]  T. Kosaka,et al.  Neuronal gap junctions between intraglomerular mitral/tufted cell dendrites in the mouse main olfactory bulb , 2004, Neuroscience Research.

[37]  Hannah Monyer,et al.  Connexin36 Mediates Spike Synchrony in Olfactory Bulb Glomeruli , 2005, Neuron.

[38]  K. Svoboda,et al.  The subcellular organization of neocortical excitatory connections , 2009, Nature.

[39]  Y. Yanagawa,et al.  Characterization of AMPA Receptors Targeted by the Climbing Fiber Transmitter Mediating Presynaptic Inhibition of GABAergic Transmission at Cerebellar Interneuron-Purkinje Cell Synapses , 2006, The Journal of Neuroscience.

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

[41]  C. Jahr,et al.  Multivesicular Release at Climbing Fiber-Purkinje Cell Synapses , 2001, Neuron.

[42]  Kenji F. Tanaka,et al.  Functional Connectome of the Striatal Medium Spiny Neuron , 2011, The Journal of Neuroscience.

[43]  Zev Balsen,et al.  Sensory Neuron Signaling to the Brain: Properties of Transmitter Release from Olfactory Nerve Terminals , 2004, The Journal of Neuroscience.

[44]  Richard Axel,et al.  Spontaneous Neural Activity Is Required for the Establishment and Maintenance of the Olfactory Sensory Map , 2004, Neuron.