The present proposal is a request for an ADAMHA RSDA Level II award for the PI to develop skills needed in an ongoing, programmatic investigation of the neural mechanisms of feeding and body weight regulation. For the immediate future, this research goal takes the form of a series of structure-function analyses of the vagus nerve. Extensive evidence has recently established that the vagus. the Xth cranial nerve, Is importantly involved in food intake and body energy regulation. Currently, however, continued progress in analyzing the relevant vagal mechanisms is seriously hampered by a lack of information about the organization of the vagal brainstem nuclei, the distribution of the vagal fibers in the digestive tract and abdominal organs, and the architecture of the forebrain and brainstem mechanisms controlling the different vagal outflows coordinating digestion and energy handling. The immediate experimental goal of the proposal is the completion of a series of promising analyses, begun during the last period, that are characterizing the organization of the last three neuronal relays in the parasympathetic outflow (i.e. the postganglionics, preganglionics. and afferents to the preganglionics) controlling the visceral organs of digestion and metabolism. Two major sets of experiments designed to provide a foundation for later. more focused functional analyses are proposed. Both sets will employ highly selective vagotomies, double and triple labeling with neural tracers, and high resolution quantitative microscopy strategies, as well as physiological analyses. The immediate research development and professional growth goals of the proposal involve a vigorous continuing education program for the PI, consisting of a number of short courses and workshops as well as visits to other laboratories. The training will be focused on the latest techniques of tracer technology, immunohistochemistry, quantitative microscopy, 3-D morphometry. Additionally, the release time will foster further professional growth by reducing the fragmentation of the PI's agenda and yielding coherent blocks of time for concentrating on research and review projects. The program outlined will extend our understanding of major neural mechanisms of obesity, diabetes, anorexia, peptic ulcers, and eating disorders. These metabolic and digestive disorders not only compromise mental health, many of them--caused or exacerbated over the pathways under investigation--are expressions of different mental health disorders.
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