Obesity accounts for significant morbidity in the USA and Western societies in general. Consumption of excess calories is a major contributing factor to the development of obesity. Consequently, understanding the neural controls of food intake is an important consideration for dealing with the development of obesity. Clearly, people eat in response to a variety of stimuli - physiological, environmental, emotional and social. However, the termination of food intake usually involves sensory signals from the viscera. Viscerosensory signals from the stomach and intestine provide important direct control of food intake. For example, both mechanical stimulation of the stomach, and chemical stimulation of the intestine provide negative feedback that contributes to termination of food intake (satiation). Although vagal sensory neurons are known to carry both gastric mechanosensitive and intestinal chemosensitive signals to the brain, nothing is known about the neurotransmitters and receptors that communicate these signals from the vagus, to and through the brain. Recently the applicant demonstrated that ionotropic, N-methyl-D-aspartate receptors (NMDA receptors) participate in termination of food intake. Additional observations suggest that NMDA receptors may specifically participate in satiety signaled by viscerosensory feedback. In support of this suggestion, preliminary results are presented indicating that NMDA receptors involved in termination of feeding are located in the dorsal hindbrain, where vagal sensory fibers from the gastrointestinal tract terminate. These results raise the intriguing possibility that NMDA receptors participate in receipt and/or integration of viscerosensory satiety signals within the first few central synapses. Accordingly, the overall goal of the experiments proposed in this application is to identify the nature of viscerosensory satiety signals, mediated by NMDA receptors and to locate the anatomical site(s) at which NMDA receptor participation in satiety occurs. In this work we will use intracranial injection technology will be used in combination with physiological manipulations of the gastrointestinal tract to locate the site of NMDA receptor participation in satiation and to analyze the physiological signals mediated by NMDA receptors in the rat.
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