AUTONOMIC CONTROLS OF BODY WEIGHT AND FEEDING

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The proposed project continues a programmatic investigation of the neural mechanisms underlying the control of feeding and body weight regulation. The long-range goal of the project is a comprehensive functional neuroanatomy of homeostasis. For the immediate future, this goal takes the form of a series of structure-function analyses of the vagus verve. Extensive behavioral and physiological 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 vagal mechanisms implicated in ingestive behavior and physiology 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. Hence, the immediate goal of the proposal is the completion of a series of promising analyses, begun during the last period, that are more fully characterizing the topographic and other organizational principles 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: The first set will generate separate inventories of the postganglionic targets, the distribution patterns, and the types of terminal profiles for the different pools of motor neurons in the dorsal motor nucleus of the vagus. Additionally, the distributions of the vagal afferents in the abdominal organs will be mapped simultaneously. The second set will begin to delineate the different CNS afferent projections to, and the local circuitry controlling, the identified pools of motor neurons within the dorsal motor nucleus of the vagus. Both sets of experiments will employ highly selective vagotomies, double and triple labeling with neural tracers, and high resolution quantitative microscopy strategies, as well as physiological analyses. The program outlined will extend our understanding of major neural mechanisms implicated in metabolic and digestive diseases including obesity, diabetes, anorexia, disorders of swallowing, vagal dysfunction, peptic ulcers, and eating disorders.