As a forebrain cortical region, the olfactory bulb is of special interest for the neural basis of smell perception. The new proposal builds on current work that has revealed new aspects of olfactory bulb circuits: their local organization in relatively narrow clusters of cells (columnar glomerular units) connected to individual glomeruli, the long distance interactions between these clusters to form glomerular unit ensembles for processing glomerular odor maps during odor stimulation, and their organization in the olfactory cortex. We will pursue analysis of these new aspects functional and anatomical approaches. First, we will use a new mouse model to monitor the stimulus of a single glomerulus, and record the spatiotemporal neural activity that arises from the local stimulus. Second, the Fos activation patterns after single glomerular stimulation will be examined. Third, we will use the pseudorabies virus as a retrograde tracer to reveal the route and reproducibility of distributed glomerular unit organization. Finally, the patterns of anatomical and functional connectivity will be examined using four complementary methods: calcium wave activation patterns, Fos staining after electrical stimulation, dextran dye tracing, and pseudorabies virus transsynaptic tracing. Together, these studies will provide a uniquely coordinated multidisciplinary test of the current hypothesis that odor processing involves activation of olfactory glomerular units in a widely distributed non-topographical manner, and the relationship of these patterns to olfactory cortex. The results will therefore suggest new principles for the functioning of cortical modules, and for the neural basis of normal odor processing.
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