Preoptic BRS3 neurons increase body temperature and heart rate via multiple pathways.

The preoptic area (POA) is a key brain region for regulation of body temperature (Tb), dictating thermogenic, cardiovascular, and behavioral responses that control Tb. Previously characterized POA neuronal populations all reduced Tb when activated. Using mice, we now identify POA neurons expressing bombesin-like receptor 3 (POA) as a population whose activation increased Tb; inversely, acute inhibition of these neurons reduced Tb. POA neurons that project to either the paraventricular nucleus of the hypothalamus or the dorsomedial hypothalamus increased Tb, heart rate, and blood pressure via the sympathetic nervous system. Long-term inactivation of POA neurons caused increased Tb variability, overshooting both increases and decreases in Tb set point, with RNA expression profiles suggesting multiple types of POA neurons. Thus, POA neuronal populations regulate Tb and heart rate, contribute to cold defense, and fine-tune feedback control of Tb. These findings advance understanding of homeothermy, a defining feature of mammalian biology.