An important challenge in developmental neurobiology is to unravel mechanisms responsible for the influences exerted by afferent innervation on the development of its targets. Good examples of such phenomena are found in the olfactory system. In the brains of all species studied to date, development of the primary olfactory center with its characteristic array of synaptic glomeruli depends dramatically on innervation by primary- afferent axons of olfactory receptor cells. How sensory axons control the formation of glomeruli, and how odotopy -- the orderly spatial representation of attributes of odor molecules -- arises in the glomerular array, are pressing problems. This project will focus on the development of individual glomeruli and their uniglomerular projection neurons, endowed with characteristic """"""""molecular receptive range"""""""" properties and will take advantage of a remarkable model system, the sexually dimorphic olfactors lobe in the brain of Manduca sexta. In particular, we will investigate the postembryonic development of the prominent macroglomerular complex in the male's olfactory lobes. This unique complex receives primary-afferent inputs solely from male-specific olfactory receptor cells, which induce the formation of the macroglomerular complex and are specialized to detect individual components of the female's sex-pheromone blend. The complex comprises two glomerular substructures, each of which receives and processes primary-afferent input about a different one of the two key components of the blend. These identified, odotopically defined glomeruli also contain neurites of male-specific central neurons, most notably uniglomerular projection neurons, which participate in specialized synaptic circuitry for processing sensory input about pheromone.
As specific aims, the proposed studies ask: (1) how the macroglomerular complex develops, (2) what role(s) glial cells play in its development, (30 whether there are quantitative and temporal requirements for male-afferent control of its development, and (4) whether male-specific sensory axons have molecular specializations that might be responsible for induction of the macroglomerular complex. The ultimate goals of the line of research represented by this proposal are; (a) to ascertain the cellular and molecular mechanisms underlying the decisive role of sensory axons in the development of glomeruli, (b) to discover how primary-afferent and central elements ultimately destined to have similar, distinctive molecular receptive ranges come to associate with each other, and (c) to determine whether glial cells participate in the development of all of the glomeruli in a particular species. This is the first effort, in any species, to ascertain developmental processes and mechanisms underlying morphogenesis of anatomically identified olfactory glomeruli with known functional specificity. This research promises to add significantly to understanding of cell-cell interactions in the development of functionally specialized, modular neuropil in the central nervous system and thus to fuel progress toward improved understanding and treatment of developmental disorders of sensory systems.

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University of Arizona
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