Cholinergic Basal Forebrain Signaling in Body Weight Homeostasis

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DESCRIPTION (provided by applicant): Obesity-associated diseases such as cardiovascular disease and diabetes account for the leading causes of death in the United States. In addition, eating disorders such as anorexia and bulimia nervosa affect millions of people worldwide. Feeding behavior is largely regulated in the brain, which integrates diverse signals from throughout the body in order to modulate the body's response to eat. Perturbations to the brain circuits that regulate this process contribute to the pathogenesis of eating and metabolic disorders. Therefore, fully understanding the brain's role in regulating food intake is essential fr developing effective therapies to treat these disorders. Towards this goal, we have recently discovered that loss of cholinergic neurons from the basal forebrain leads to increased food intake and severe obesity in adult mice. Furthermore, we have shown that these neurons project to, and receive input from, the hypothalamus, a major control center of feeding behavior. Using innovative techniques in genetics, physiology, and behavioral testing, we propose to determine the role of cholinergic basal forebrain signaling on body weight homeostasis. Specifically, we propose to (1) determine the effect of impaired or enhanced cholinergic basal forebrain signaling on food intake, energy expenditure, and feeding- associated peptide signaling, and (2) map, characterize, and mechanistically determine the neuronal brain circuits involved in cholinergic-mediated effects on feeding behavior and body weight homeostasis.