Defining locus coeruleus-norepinephrine (LC-NE) circuits in feeding
PROJECT SUMMARY Overeating is a major contributor to excessive weight gain, involving the hypothalamus and innervating brain systems that control reward, motivation, learning and emotion. Accumulating clinical data indicate that disruptions to the norepinephrine (NE) signaling system underlie key aspects of obesity. NE stimulants are currently the most effective therapies for weight loss, but the precise neural circuits that underlie this regulation of feeding remain largely unresolved. The goal of this proposed K99-R00 research is to dissect the role of the locus coeruleus (LC) to lateral hypothalamus (LHA) noradrenergic circuit in feeding and dietary obesity. The central hypothesis is that increased LC-NE activity will suppress feeding through inhibition of LHA hunger- promoting neurons. The basis for this hypothesis comes from the candidate’s preliminary data, together with published findings. To test the central hypothesis, the candidate will carry out three Specific Aims: (1) Iden