Metabotropic glutamate receptors (mGluRs) are densely expressed by the major cell types of the main olfactory bulb (MOB), yet their functional role(s) in olfactory processing remain poorly understood. During the previous funding cycle, studies from our lab demonstrated that activation of mGluRs directly enhances the excitability of mitral cell and granule cells. New preliminary data suggest that specific mGluR subtypes (mGluRI and mGluRS) are differentially expressed by morphologically discrete subpopulations of GABAergic granule cells. Based on these and other new findings, we hypothesize that activation of mGluRI and mGluRS differentially modulates short vs. long-range lateral inhibition in the MOB via the mitral cell-to granule cell dendrodendritic circuit. This hypothesis will be tested using patch clamp electrophysiology in mice MOB slices. The role of mGluRs in intraglomerular processing is unknown. New preliminary studies demonstrate that activation and inactivation mGluRs potently modifies the spontaneous and sensory evoked excitability of external tufted (ET) cells in the glomerulus. Activation of mGluRs also enhances electrotonic coupling between ET cells and leads to the emergence of slow rhythmic activity in the glomerular layer. Based on these and other new findings, we hypothesize that activation of mGluRs on ET cells enhances synchrony in the glomerular network and leads to the emergence of slow rhythmic oscillations in mitral cells that are linked to respiratory-driven sensory input to the MOB. Additional findings demonstrate that mGluRs also enhance intraglomerular GABAergic inhibition of ET cells. These hypotheses will be tested at the cellular and circuit level using patch clamp electrophysiology in MOB slices from wildtype mice, as well as slices from mice with targeted gene deletions of the major mGluR expressed by MOB neurons. The overarching goal of this proposal is to elucidate the roles of mGluRs in the operation of the MOB network and odor coding. It is hoiped that a better understanding of the normal operation of the olfactory system will aid in the treatment or prevention of olfactory impairments that occur with aging and in certain neurodegenerative disorders.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Somatosensory and Chemosensory Systems Study Section (SCS)
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Sullivan, Susan L
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University of Tennessee Health Science Center
Anatomy/Cell Biology
Schools of Medicine
United States
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Dong, Hong-Wei; Ennis, Matthew (2014) Activation of group I metabotropic glutamate receptors enhances persistent sodium current and rhythmic bursting in main olfactory bulb external tufted cells. J Neurophysiol 111:641-7
Dong, Hong-Wei; Davis, James C; Ding, ShengYuan et al. (2012) Expression of transient receptor potential (TRP) channel mRNAs in the mouse olfactory bulb. Neurosci Lett 524:49-54
Nai, Q; Dong, H W; Linster, C et al. (2010) Activation of alpha1 and alpha2 noradrenergic receptors exert opposing effects on excitability of main olfactory bulb granule cells. Neuroscience 169:882-92
Nai, Qiang; Dong, Hong-Wei; Hayar, Abdallah et al. (2009) Noradrenergic regulation of GABAergic inhibition of main olfactory bulb mitral cells varies as a function of concentration and receptor subtype. J Neurophysiol 101:2472-84
Dong, Hong-Wei; Heinbockel, Thomas; Hamilton, Kathryn A et al. (2009) Metabotropic glutamate receptors and dendrodendritic synapses in the main olfactory bulb. Ann N Y Acad Sci 1170:224-38
Dong, Hong-Wei; Hayar, Abdallah; Callaway, Joseph et al. (2009) Group I mGluR activation enhances Ca(2+)-dependent nonselective cation currents and rhythmic bursting in main olfactory bulb external tufted cells. J Neurosci 29:11943-53
Heinbockel, Thomas; Laaris, Nora; Ennis, Matthew (2007) Metabotropic glutamate receptors in the main olfactory bulb drive granule cell-mediated inhibition. J Neurophysiol 97:858-70
Laaris, Nora; Puche, Adam; Ennis, Matthew (2007) Complementary postsynaptic activity patterns elicited in olfactory bulb by stimulation of mitral/tufted and centrifugal fiber inputs to granule cells. J Neurophysiol 97:296-306
Dong, Hong-Wei; Hayar, Abdallah; Ennis, Matthew (2007) Activation of group I metabotropic glutamate receptors on main olfactory bulb granule cells and periglomerular cells enhances synaptic inhibition of mitral cells. J Neurosci 27:5654-63
Heinbockel, Thomas; Hamilton, Kathryn A; Ennis, Matthew (2007) Group I metabotropic glutamate receptors are differentially expressed by two populations of olfactory bulb granule cells. J Neurophysiol 97:3136-41

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