Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide (CGRP) in the parabrachial nucleus (PBN) relay sensory signals that contribute to satiation and pain-induced fear behavior, but it is unknown how they encode these distinct processes. By recording calcium transients in vivo from individual CGRPPBN neurons, we reveal that most neurons are activated by noxious cutaneous (shock, heat, itch) and visceral stimuli (lipopolysaccharide). These same neurons are inhibited during feeding, but become activated during satiation, consistent with evidence that CGRPPBN neurons prevent overeating. CGRPPBN neurons are also activated during consumption of novel food or by an auditory cue that was previously paired with electrical foot shocks. Correspondingly, silencing CGRPPBN neurons attenuates expression of food neophobia and conditioned fear responses. Therefore, in addition to transducing primary sensory danger signals, CGRPPBN neurons promote affective-behavioral states that limit harm in response to potential threats.

SUMMARY 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.