The proposed project will continue a programmatic investigation of the autonomic neural mechanisms of feeding and body weight regulation. The long-range goal of the project is to obtain information critically needed for treating ingestive disorders, notably obesity, and a variety of gastrointestinal (Gl) diseases. The vagus nerve is the major neural pathway reciprocally connecting the brain and the Gl tract. Vagal sensory and motor axons coordinate much of the physiology of energy homeostasis, including both short- and longterm controls of ingestion and body weight. Surprisingly, given the crucial importance of the vagus, many of the nerve's structural and functional details particularly relevant to an understanding of ingestion are as yet unknown. Thus, the goals of the project are to continue a series of productive analyses that are characterizing the morphological types, regional distributions, and functions of vagal projections that link the brain and Gl tract. The first specific aim is to characterize and map the different vagal~and other visceralsensory endings in the stomach. The second specific aim is to describe and map the vagal~and other visceral-sensory endings in the intestines. The experiments of these first two aims will use recently adapted neural tracer protocols to provide inventories of, and maps for, the chemo-, mechano-, osmo-, and thermoreceptors throughout the gut.
The third aim i s to characterize and map different vagal?and sympatheticmotor projections to the Gl tract. This series of experiments will use tracers to yield an inventory of, and maps for, the motor projections by which the brain coordinates Gl functions.
The final aim i s to evaluate alterations in ingestive behavior associated with selective remodeling ofthe innervation of the Gl tract. The experiments of this aim will use structure-function correlations in animal models involving surgical manipulations ofthe stomach and duodenum, vagal losses produced by selective mutations, vagal neuropathies, transections, and regeneration. These four specific aims are direct extensions of the four aims that have guided the research of the last five years of the project.
The aims are critical to developing treatments for obesity and other metabolic and digestive diseases. The experiments will generate a neuroscience foundation for refining obesity surgeries, now guided primarily by trial and error, and other interventions ofthe Gl tract (e.g., pacemakers) that are used to treat eating disorders, reflux disease, irritable bowel syndrome, peptic ulcers, autonomic neuropathies, and visceral pain.
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