Median Preoptic Brs3 -Expressing Neurons Regulate Heat-Evoked Defensive Escalation

Abstract Animals confronted with increasing heat must switch from exploratory behavior to vigorous actions that limit further exposure, but the forebrain circuits controlling this transition are poorly understood. We exposed male mice to progressively stronger floor heating while providing continuous access to a climbing mesh separated from the heating plate. Higher plate settings shifted behavior from rearing toward wall-directed digging and climbing, with jumping at the highest setting, and increased c-Fos labeling in the median preoptic nucleus. Neurons expressing bombesin receptor subtype 3 showed greater c-Fos recruitment under strong heating, and their population calcium signals increased when mice entered the plate-controlled zone and decreased when they left. Optogenetic activation without heating produced place avoidance, vigorous actions, and increased locomotion. Inhibition reduced locomotion and, during strong heating, shifted behavior from climbing and jumping toward rearing and weakened avoidance of a localized heat source. These findings identify median preoptic Brs3 -expressing neurons as regulators of behavioral escalation and heat avoidance.