Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia

Abstract Mammals normally maintain a constant body temperature irrespective of their environmental temperature. However, emotions such as fear can trigger acute changes in body temperature accompanying defensive behaviors to enhance survival in life-threatening conditions. The neural mechanisms of fear-associated thermoregulation remain unclear. Here, we find that innate fear odor 2-methyl-2-thiazoline (2MT) evokes rapid hypothermia and elevated tail temperature, indicative of vasodilation-induced heat dissipation, in wild-type mice, but not in mice lacking Trpa1, the chemosensor for 2MT. Following 2MT exposure, wild-type but not Trpa1-/- mice exhibit high c-fos expression in the posterior subthalamic nucleus (PSTh), external lateral parabrachial subnucleus (PBel), and nucleus of the solitary tract (NTS). Tetanus toxin light chain (TeLC)-mediated inactivation of NTS-projecting PSTh neurons blunts 2MT-evoked hypothermia and abrogated tail temperature increase. Optogenetic activation of the PSTh-rostral NTS (RNTS) pathway specifically induces hypothermia and elevated tail temperature. Moreover, selective opto-stimulation of 2MT-activated PSTh-projecting PBel neurons, by capturing activated neuronal ensembles (CANE), induces hypothermia and elevated tail temperature. Conversely, chemogenetic suppression of vGlut2+ neurons in PBel and PSTh or PSTh-projecting PBel neurons attenuates 2MT-evoked hypothermia and tail temperature increment. Taken together, these results uncover a novel PBel-PSTh-NTS neural pathway that underlies 2MT-evoked innate fear-associated hypothermia and tail vasodilation.