Cold-sensitive Ventromedial Hypothalamic Neurons Control Homeostatic Thermogenesis and Social Interaction-Associated Hyperthermia

Homeostatic thermogenesis is an essential protective feature of endotherms. However, the specific neuronal types involved in cold-induced thermogenesis remain largely unknown. Using functional magnetic resonance imaging and in situ hybridization, we screened for cold-sensitive neurons and found preprodynorphin (PDYN)-expressing cells in the dorsal medial region of the ventromedial hypothalamus (dmVMH) to be a candidate. Subsequent in vivo calcium recording showed that cold temperature activates dmVMH(Pdyn) neurons, whereas hot temperature suppresses them. In addition, optogenetic activation of dmVMH(Pdyn) neurons increases the brown adipose tissue and core body temperature, heart rate, and blood pressure, whereas optogenetic inhibition shows opposite effects, supporting their role in homeostatic thermogenesis. Furthermore, we found that dmVMH(Pdyn) neurons are linked to known thermoregulatory circuits. Importantly, dmVMH(Pdyn) neurons also show activation during mouse social interaction, and optogenetic inhibition suppresses social interaction and associated hyperthermia. Together, our study describes dual functions of dmVMH(Pdyn) neurons that allow coordinated regulation of body temperature and social behaviors.