GLOMERULI AS FUNCTIONAL UNITS FOR OLFACTORY CODING

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DESCRIPTION (adapted from applicant's abstract): The primary olfactory centers in the brains of diverse animals, including humans, are characterized by an array of synaptic modules called glomeruli. These centers are thought to be organized chemotopically, such that odor information is represented spatially among glomeruli, but this important hypothesis has not been tested comprehensively in a species offering the advantages of anatomical simplicity, identifiable glomeruli, accessible receptor cells and central neurons, and chemically identified, behaviorally relevant odors. Moreover, despite dramatic advances in chemosensory research, we still do not understand how complex odor stimuli are encoded in neural activity, within and among glomeruli, that ultimately leads to appropriate behavioral responses. This project builds on a firm foundation of technical experience and knowledge about an experimentally favorable model, the olfactory system of Manduca sexta, which is comparable to its vertebrate counterpart in organization and function and permits the hypothesis of glomerular chemotopy to be tested with greater precision than has been possible in other species. This model system also offers an exceptional opportunity to unravel the synaptic neural circuitry within and between identified glomeruli in order to reveal how specific odor information is processed at its first way-station in the brain. By means of intracellular recording and staining, extracellular multichannel recording, laser-scanning confocal and transmission electron microscopy, and computer-assisted mathematical modeling, we will focus on identified glomeruli in recognizable clusters to: (1) test the hypothesis that glomeruli are organized chemotopically by determining what chemical, temporal, and intensity properties of behaviorally significant odor stimuli are analyzed and encoded by individual neurons innervating particular glomeruli; (2) characterize synaptic circuits within and between glomeruli to learn how the various types of neurons associated with glomeruli interact to shape the signas conveyed by output neurons projecting to higher centers in the brain; and (3) develop mathematical models of characterized neurons to generate testable hypotheses about their physiology and synaptic interactions. This research will promote understanding of basic olfactory mechanisms in all animals, including mankind, and promises to contribute toward explanation of sensory disorders such as parosmia, hyposmia, and anosmia.