The proposed project continues a systematic investigation of the neural mechanisms of body weight regulation and feeding. Ample evidence now exists that the vagus nerve is importantly involved in body energy regulation and food intake. Currently, however, continued progress in analyzing the vagal mechanisms implicated in the behavior and physiology of ingestion is seriously hampered by a lack of basic information about the organization of the vagal nuclei in the brainstem, the distribution of the vagus in the abdomen, and functional patterns of vagal activity. Compounding the problem, the lack of the same information has also retarded the development of adequate tests of vagotomy or normal vagal function. The lack of these tests has, in turn, further impeded research on the precise roles of the vagus in weight regulation, feeding and related disease processes. The immediate goal is the continuation of a series of promising analyses, begun during the last period, that are delineating the organization of the vagus through the use of converging physiological, anatomical, surgical and behavioral techniques. Five sets of experiments designed to provide a foundation for later, more extended functional analyses are proposed: The first two sets consist of anatomical and physiological characterizations of the topographic organization of the vagal motor nuclei in the medulla oblongata. That information is then also applied in a high resolution test for different selective vagotomies. The next two sets employ similar experimental methods to characterize the functional organization and distribution of the individual branches of the vagus nerve in the abdomen. The fifth group of experiments, drawing on the results of the first four, includes a number of fine-grained analyses of the role of defined vagal mechanisms in the altered metabolism and food intake of different animal models. The program outlined will extend our understanding of major neural mechanisms implicated in metabolic and digestive diseases including obesity, diabetes, anorexia, vagal dysfunction, peptic ulcers, and eating disorders.
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