The overall goal of this proposal is to understand the functional mechanisms of inhibitory interneurons in the mammalian olfactory bulb. These interneurons, called granule cells and periglomerular (PG) cells, are often proposed to impact olfactory information processing in one of two ways, either by synchronizing the activity of the bulb's output neurons (mitral cells) or by mediating lateral inhibitory interactions between mitral cells. However, the functional mechanisms of the interneurons are not well-understood. Studies in the first two Specific Aims of this proposal use patch-clamp recordings from interneurons in olfactory bulb slices in order to evaluate two mechanistic aspects of interneurons that we predict are critical for function. These include the mechanisms of synaptic activation of interneurons by mitral cells (Aim 1) and mechanisms that couple the activity of different interneurons (Aim 2).
In Specific Aim 3, recordings from pairs of mitral cells in slices will be made to test the functional role of interneurons in synchronizing action potential-firing in mitral cells. A key novel aspect of our studies is our electrical stimulation paradigm. While previous studies have examined interneuron mechanisms under static conditions, we examine their functional properties under dynamic, more physiological conditions produced by low frequency stimulation of afferent olfactory nerve (ON) fibers. The results of our studies will lead to a direct understanding of how synchronized activity is generated in the bulb, and also point toward possible mechanisms that could alter such activity following olfactory learning or during pathological conditions, such as Alzheimer's and Parkinson's disease. In addition, our mechanistic studies of synchronized activity could provide insight into mechanisms of epileptogenic dysfunction in other brain circuits.

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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Davis, Barry
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University of Colorado Denver
Schools of Medicine
United States
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Pouille, Frederic; Schoppa, Nathan E (2018) Cannabinoid Receptors Modulate Excitation of an Olfactory Bulb Local Circuit by Cortical Feedback. Front Cell Neurosci 12:47
Pouille, Frederic; McTavish, Thomas S; Hunter, Lawrence E et al. (2017) Intraglomerular gap junctions enhance interglomerular synchrony in a sparsely connected olfactory bulb network. J Physiol 595:5965-5986
Bourne, Jennifer N; Schoppa, Nathan E (2017) Three-dimensional synaptic analyses of mitral cell and external tufted cell dendrites in rat olfactory bulb glomeruli. J Comp Neurol 525:592-609
Shen, Chong; Rathore, Shailendra S; Yu, Haijia et al. (2015) The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis. Nat Commun 6:8852
Zak, Joseph D; Whitesell, Jennifer D; Schoppa, Nathan E (2015) Metabotropic glutamate receptors promote disinhibition of olfactory bulb glomeruli that scales with input strength. J Neurophysiol 113:1907-20
Sheridan, D C; Hughes, A R; Erdélyi, F et al. (2014) Matching of feedback inhibition with excitation ensures fidelity of information flow in the anterior piriform cortex. Neuroscience 275:519-30
Whitesell, Jennifer D; Sorensen, Kyle A; Jarvie, Brooke C et al. (2013) Interglomerular lateral inhibition targeted on external tufted cells in the olfactory bulb. J Neurosci 33:1552-63
Gire, David H; Franks, Kevin M; Zak, Joseph D et al. (2012) Mitral cells in the olfactory bulb are mainly excited through a multistep signaling path. J Neurosci 32:2964-75
Gire, David H; Schoppa, Nathan E (2009) Control of on/off glomerular signaling by a local GABAergic microcircuit in the olfactory bulb. J Neurosci 29:13454-64
Luna, Victor M; Schoppa, Nathan E (2008) GABAergic circuits control input-spike coupling in the piriform cortex. J Neurosci 28:8851-9

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