Glomeruli as Functional Units for Olfactory Coding

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DESCRIPTION (provided by applicant): 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 organized chemotopically, such that odor information is represented spatially among glomeruli. Despite dramatic advances in chemosensory research, we still do not understand how information about odor stimuli is encoded in neural activity, within and among glomeruli, before being relayed to higher-order cortical areas for further processing. 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 mammalian counterpart in organization and function and permits neurophysiological testing of hypotheses about glomerular processing of odor information with greater precision than has been possible in other species. This model system offers the advantages of anatomical simplicity, identifiable glomeruli, accessible receptor cells and central neurons, and chemically identified, behaviorally relevant odors. It also offers an exceptional opportunity to unravel synaptic neural circuitry within and among identified glomeruli in order to analyze 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 microscopy, and cloning, expression and pharmcological studies of key synaptic receptors, we will focus on identified "reference" glomeruli of known odor "tuning" and their neighboring glomeruli to test the hypotheses that: (1) the projection (output) neurons (PNs) of a glomerulus are functionally diverse; (2) functional similarity of PNs correlates with enhanced firing synchrony; (3) intra- and interglomerular synaptic circuitry, and especially inhibitory connections, shape the activity of PNs, including synchrony of firing, and thus is key to understanding central coding and integration of odor information; and (4) synaptic interactions between glomeruli are strongest between adjacent glomeruli. 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.