Parabrachial CGRP Neurons Control Meal Termination

• Published in: Cell metabolism Vol. 23; no. 5; pp. 811 - 820
• Main Authors: Campos, Carlos A., Bowen, Anna J., Schwartz, Michael W., Palmiter, Richard D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.05.2016
• Subjects: Agouti-Related Protein - metabolism; Animals; Anorexia - metabolism; Anorexia - pathology; Calcitonin Gene-Related Peptide - metabolism; Central Amygdaloid Nucleus - metabolism; Cholecystokinin; Feeding Behavior; Glucagon-Like Peptide-1 Receptor - metabolism; Glucagon-Like Peptide-1 Receptor Agonists; Hyperphagia - metabolism; Hyperphagia - pathology; Leptin; Mice, Inbred C57BL; Neurons - metabolism; Parabrachial Nucleus - metabolism; Satiety Response
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2016.04.006

The lateral parabrachial nucleus is a conduit for visceral signals that cause anorexia. We previously identified a subset of neurons located in the external lateral parabrachial nucleus (PBel) that express calcitonin gene-related peptide (CGRP) and inhibit feeding when activated by illness mimetics. We report here that in otherwise normal mice, functional inactivation of CGRP neurons markedly increases meal size, with meal frequency being reduced in a compensatory manner, and renders mice insensitive to the anorexic effects of meal-related satiety peptides. Furthermore, CGRP neurons are directly innervated by orexigenic hypothalamic AgRP neurons, and photostimulation of AgRP fibers supplying the PBel delays satiation by inhibiting CGRP neurons, thereby contributing to AgRP-driven hyperphagia. By establishing a role for CGRP neurons in the control of meal termination and as a downstream mediator of feeding elicited by AgRP neurons, these findings identify a node in which hunger and satiety circuits interact to control feeding behavior. [Display omitted] •Parabrachial CGRP neurons contribute to physiological control of appetite•Inactivation of CGRP neurons decreases perception of meal-induced satiety signals•Hunger-activated AgRP neurons are connected to and inhibit CGRP neurons•CGRP neurons constrict feeding elicited by AgRP neuron activation Campos et al. show that parabrachial CGRP neurons transduce meal-related satiety signals and inactivation of these neurons impairs the ability of mice to terminate meals. CGRP neurons are also inhibited by orexigenic AgRP neurons, and concurrent activation of AgRP neurons and silencing of CGRP neurons leads to uncontrolled feeding.