Genetically Dissecting Basal Forebrain Circuits Underlying Eating Disorders
Abstract
Abnormal eating habits that drive excessive food seeking -- or avoidance -- can manifest as health-threatening and socially impactful eating disorders. Comorbidity often exists between eating disorders and stress, an emotional state tightly associated with military personnel and their families. To date, studies investigating the neural contribution to eating habits and body weight control have focused largely on neuropeptidergic signaling in the hypothalamus, a key brain region involved in feeding behavior. However, signaling from extra-hypothalamic brain regions has also been implicated in regulating nutrient metabolism, appetite, and satiety. We have previously reported a potent role for cholinergic neurons in the basal forebrain in regulating feeding behavior, and we recently discovered that cell type-specific manipulations of their immediate downstream targets are capable of directly toggling a spectrum of eating-associated behaviors that range from increased food seeking, excessive food consumption, and obesity, to severe hypophagia, food avoidance, and starvation. Circuits that govern feeding behavior overlap with those involved in reward, aversion, and addiction, and the basal forebrain has been closely linked to each of these states. Thus, our previous findings and preliminary data strongly implicate the basal forebrain as a critical modulator of feeding behavior. Using multifaceted genetic, electrophysiological, imaging, optogenetic, and behavioral experimentation, we propose studies that will help elucidate the critical, and yet unknown, mechanisms by which the basal forebrain-to-hypothalamic circuit influences control of eating and associated emotional states. Importantly, the proposed research will help reveal previously unidentified components of feeding circuits and provide new insight into the convergent mechanisms of how cholinergic and hypothalamic circuits intersect to influence feeding drive, metabolism, and features of addiction. Our results will also reveal key circuit bases for feeding abnormalities associated with smoking and nicotine use, which often occurs in Service members and Veterans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910429
Entities
People
- Qingchun Tong
Organizations
- United States Army
- University of Texas Health Science Center at Houston