The intestinal mucosa of the hibernator appears to maintain absorptive capacity until spring emergence despite the lack of luminal nutrition during hibernation. In contrast, fasting in non- hibernating mammals results in a significant reduction in absorptive function after 3 days. The aims of this project are to determine if seasonal variations in intestinal nutrient and electrolyte transport occur during the annual cycle for the hibernating ground squirrel, and to identify the mechanisms and signals that lead to adaptive regulation of intestinal transport function during the annual cycle. Intestinal sugar and electrolyte transport will be assessed in ground squirrels during the spring, summer, fall and winter. Winter studies will involve hibernating squirrels as well as squirrels that were allowed to remain active and feeding in a warm room. Transepithelial fluxes of glucose, sodium and chloride will be measured in jejunal segments set up in modified Ussing-type chambers. Glucose influx across the brush border membrane will be measured to determine if changes in the number of glucose carrier sites or the affinity of glucose for its carrier are responsible for adaptive changes in transport function. Intestinal mass and structure in each group of squirrels will be estimated by measuring the weights, protein and DNA content, and villus and crypt dimensions of mucosa harvested from segments adjacent to those used in the physiological experiments. Blood and tissue samples will be collected from squirrels used in the transport experiments for later analysis of peptides and other messengers that might be involved in seasonal changes in intestinal structure and function. Pharmacological and histological tools will be used to identify the signals that mediate the mucosal response to enteric neural stimulation. These studies are expected to provide insight into the natural rhythms of the gastrointestinal tract and the signals that lead to adaptive regulation during hibernation.