The sense of smell is the principal window on the rich and complex world of volatile chemicals. The main and accessory olfactory systems of mammals serve to detect and analyze odors and pheromones. However, it is becoming clear that the division of nasal chemosensory neurons into only these two groups is simplistic and does not reflect the functional diversity of receptor cell types in the nose. A novel group of chemosensory neurons, which target a unique population of glomeruli, the """"""""necklace"""""""" glomeruli, in the posterior olfactory bulb, are found in several regions of the main olfactory epithelium. These neurons also exhibit a gene expression profile distinct from that of other chemosensory neurons. However, it is unclear if these receptor neurons and glomeruli function as a distinct chemosensory system. We have created a gene-targeted mouse that functionally disrupts the gene encoding the guanylyl cyclase, GC-D, a protein critical for the function of these cells. After targeting, this gene locus also encodes a histochemical reporter, tau-beta-galactosidase that permits the visualization of the neurons that express GC-D. We propose to use this mouse model to perform the first systematic analysis of the organization and functional characteristics of this poorly understood population of chemosensory neurons, as well as to characterize the functional role of these cells in chemosensory behavior. We will provide a systematic anatomical description of these neurons and the necklace glomeruli and determine the developmental and anatomical expression patterns of GC-D in the olfactory system. We will also determine the chemosensory role of these neurons through behavioral and biochemical analyses of adult and neonatal animals. Finally, we will characterize the biochemical cascade involved in the transduction of specific chemosensory stimuli, including both odors and pheromones, in these cells. These results obtained in these studies will provide important insights into the mechanism by which these neurons and glomeruli detect and analyze sensory stimuli, the role of cGMP signaling in these processes, and will define the sensory role of this unique neuronal population.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
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Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
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Davis, Barry
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University of Maryland Baltimore
Anatomy/Cell Biology
Schools of Medicine
United States
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Uytingco, Cedric R; Puche, Adam C; Munger, Steven D (2016) Interglomerular Connectivity within the Canonical and GC-D/Necklace Olfactory Subsystems. PLoS One 11:e0165343
Uytingco, Cedric R; Puche, Adam C; Munger, Steven D (2016) Using Intrinsic Flavoprotein and NAD(P)H Imaging to Map Functional Circuitry in the Main Olfactory Bulb. PLoS One 11:e0165342
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Arakawa, Hiroyuki; Cruz, Stephanie; Deak, Terrence (2011) From models to mechanisms: odorant communication as a key determinant of social behavior in rodents during illness-associated states. Neurosci Biobehav Rev 35:1916-28
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Zufall, Frank; Munger, Steven D (2010) Receptor guanylyl cyclases in mammalian olfactory function. Mol Cell Biochem 334:191-7

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