Disruption of Pre-Botzinger Complex neuropeptidergic tonality controls fear and metabolic response.

ABSTRACT: Stress profoundly impacts systemic metabolism, yet the central circuits linking stress responses to peripheral metabolic regulation remain poorly defined. Here, we identify the preBötzinger complex (preBötC), a brainstem breathing rhythm generator, as a key stress-responsive hub coordinating metabolic adaptations. Using viral tracing, we show that preBötC neurons project to brown adipose tissue and liver, and that a subset of these projection neurons expresses the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor PAC1R, positioning PACAP signaling as a critical modulator of this circuit. Whole-brain c-Fos mapping revealed robust preBötC activation under stress, while spatial transcriptomics demonstrated altered neuronal metabolic circuitry in preBötC following PAC1R ablat

SUBMITTER: Shetty S 

PROVIDER: S-EPMC12776275 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature