Role of Parabrachial Nucleus Neuropeptides in Feeding

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DESCRIPTION (provided by applicant): Feeding and metabolic disorders such as obesity, anorexia, bulimia, failure to thrive, gastric reflux, cachexia, early satiety, delayed gastric emptying, dysgeusia, and anosmia contribute to diseases including hypertension, stroke, diabetes, and heart disease, and account for many health-care costs. Elucidating the neural systems that control feeding is a fundamental goal for clinical as well as basic science. Studies have identified brain areas that are sensitive to hormones that affect feeding and adiposity: leptin, ghrelin, and insulin. Scientists have identified neuropeptides in the brain that are sensitive to these hormones and act as downstream mediators to influence feeding and metabolism. These neuropeptides, such as neuropeptide Y (NPY), and melanin-concentrating hormone (MCH), act or have receptors in forebrain and hindbrain locations. An important goal for future research is to determine how such neuropeptides function in brainstem nuclei and to determine how these nuclei interact with forebrain nuclei (e.g., hypothalamus) that are sensitive to leptin, ghrelin, and insulin. This proposal will evaluate the effects of MCH and NPY on feeding and electrophysiological taste and visceral responses in the pontine parabrachial nucleus (PBN), a brainstem nucleus that receives significantly overlapping taste and visceral afferent inputs, receives direct NPY and MCH input from the hypothalamus, and sends output to brainstem nuclei controlling oral movement. The first experiments assess effects of direct PBN microinjectons of MCH and NPY and respective antagonists on feeding microstructure. Following experiments assess the effects of MCH and NPY on neural PBN gustatory and gastric distension responses when MCH and NPY and respective antagonists are applied to brain ventricles or microinjected directly around PBN neurons. If direct PBN application of MCH or NPY affects feeding, this should be observed at the neurophysiological level and will serve to better clarify the functional role(s) of hypothalamic neuropeptides in the brainstem.