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.
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