The proposed project continues a programmatic investigation of the neural mechanisms of feeding and body weight regulation. The long-range goal of the project is to provide information 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-term and long-term controls of ingestion and body weight. Surprisingly, given the crucial importance of the vagus, many of the nerve's structural and functional features particularly relevant to an adequate understanding of ingestion are as yet undescribed. Thus, the immediate goal of the project is to conduct a series of promising 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 visceral - sensory 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 thermo- receptors throughout the gut.
The third aim i s to characterize and map different vagal motor projections to the Gl tract. This third 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 structural changes in the innervation of the Gl tract. The experiments of this aim will use structure-function correlations in animal models involving vagus nerve transections and regeneration, vagal losses produced by selective mutations, and surgical manipulations of the stomach and duodenum.
The aims are critically relevant to developing treatments for obesity and other metabolic and digestive diseases. The proposed experiments will generate a more adequate neuroscience foundation for refining obesity surgeries (e.g., bypasses and pacemaker implants), now designed primarily through trial and error, and other interventions of the Gl tract that are used in the treatment of eating disorders, reflux disease, irritable bowel syndrome, peptic ulcers, autonomic neuropathies, and visceral pain. ? ? ?
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