Oxytocin neurons signal state-dependent transitions to thermogenesis and behavioral arousal in social and non-social settings

Abstract

Mammalian thermoregulatory behaviors such as thermal comfort seeking, physical activity, nesting, and huddling operate alongside autonomic responses such as brown fat thermogenesis and peripheral vasodilation to defend core body temperature (Tb)1–4. The defended Tb is not held constant, but alternates across active/rest and behavioral cycles5–9. Although the thermoregulatory behaviors facilitating these alternations are controlled by the brain, the underlying neural populations are poorly understood. The oxytocin system has been proposed to contribute to behavioral thermoregulation10,11, yet evidence for how activity within oxytocin neurons relates to such pathways is lacking. Here, we identify neuronal dynamics underlying behavioral thermoregulation in mice. We show that the paraventricular hypothalamus (PVN) and PVN oxytocin (PVNOT) neurons are selectively activated during two thermoregulatory states: active and quiescent huddling. Next, activation and inhibition of PVNOTneurons reveals effects on Tb, peripheral vasodilation, and warm seeking, establishing a role in thermoeffector pathways. We then demonstrate that in vivo PVNOTcalcium activity tracks the patterning of thermoregulatory behaviors. Across social contexts, PVNOTpeaks occur during low Tb (~36.0°C) and during transitions towards physical activity and thermogenesis. In the solo context, PVNOTpeaks predict the offset of quiescence and onset of post-quiescence nesting. In the paired context, PVNOTpeaks predict the offset of quiescent huddling and onset of post-quiescent active huddling. Our study provides evidence for a role of PVNOTneurons during the offset of rest and the onset of behavioral arousal and thermogenesis and provides a foundation for understanding the coordination between thermal homeostasis and animal behavior.