Tuesday, June 17, 2025
6/17/2025
Autonomic Control of Body Weight and Feeding - Recent increases in the epidemics of obesity, diabetes, and both eating and gastrointestinal (GI) disorders underscore the fact that adequate treatments have yet to be developed. As the NIH BRAIN initiative and other programs have stressed, the underlying brain‐gut circuitry must be characterized if clinical interventions are to be developed efficiently. The overall goal of the current research program is to use state‐of‐the‐art neuroscience protocols to characterize those brain‐gut pathways. While the present project has made important progress delineating the autonomic projections to the outer smooth muscle wall of the esophagus, stomach,and intestines, characterizations of the elements of vagal and other autonomic circuitry that innervate the inner mucosal and submucosal linings of the intestines have yet to be accomplished. This lack of information for the inner wall of the intestines is problematic, since the vagal sensory innervation of the mucosal lining of the GI tract is fundamental for integrating the information and patterns of nutrient fluxes, caloric densities, paracrine signaling, and microbiome dynamics that collectively control ingestion, digestion, absorption, and metabolism of nutrients. In two complementary series of experiments organized as two Specific Aims, the present renewal request proposes to generate comprehensive foundational descriptions of the vagal sensory projections to the mucosa and submucosa of the intestines. Specific Aim 1 proposes a set of six cumulative experiments to phenotype, determine 3D architectural morphometry, map topographically, and establish the surgical approach to the recently described vagal crypt endings that innervate the intestinal glands. SA 1 will also compare the morphology of the crypt endings in males and females and assess remodeling of the endings as a function of maintenance on an obesogenic high fat diet. Specific Aim 2 proposes a parallel set of experiments chacterizing the phenotype, 3D morphometry, maps, and vagal pathways of the vagal villus arbors that innervate the epithelial walls of intestinal villi. In sum, the present project will provide fundamental observations on the sensory elements of the brain‐intestines axis that are immediately involved in integrating the GI signals controlling metabolism.
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