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

Can Liu,Can Liu,Can Liu,Qinghua Liu,Qinghua Liu,Qinghua Liu,Qinghua Liu,Peng Cao,Peng Cao,Katsuyasu Sakurai,Greg Asher,Greg Asher,Yuka Terakoshi,Yuka Terakoshi,Liqin Cao,Liqin Cao,Reiko Kobayakawa,Ko Kobayakawa,Chia-Ying Lee,Chia-Ying Lee

doi:10.1038/s41467-021-22914-6

Abstract

The neural mechanisms of fear-associated thermoregulation remain unclear. Innate fear odor 2-methyl-2-thiazoline (2MT) elicits 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. Here we report that Trpa1−/− mice show diminished 2MT-evoked c-fos expression in the posterior subthalamic nucleus (PSTh), external lateral parabrachial subnucleus (PBel) and nucleus of the solitary tract (NTS). Whereas tetanus toxin light chain-mediated inactivation of NTS-projecting PSTh neurons suppress, optogenetic activation of direct PSTh-rostral NTS pathway induces hypothermia and tail vasodilation. Furthermore, selective opto-stimulation of 2MT-activated, PSTh-projecting PBel neurons by capturing activated neuronal ensembles (CANE) causes hypothermia. Conversely, chemogenetic suppression of vGlut2+ neurons in PBel or PSTh, or PSTh-projecting PBel neurons attenuates 2MT-evoked hypothermia and tail vasodilation. These studies identify PSTh as a major thermoregulatory hub that connects PBel to NTS to mediate 2MT-evoked innate fear-associated hypothermia and tail vasodilation.

Highlights

The neural mechanisms of fear-associated thermoregulation remain unclear
We demonstrated that Trpa[1], a well-known receptor for pungent/irritant chemicals, functions as a chemosensor for 2MT/TMT and that transient receptor potential A1 (Trpa1)+ trigeminal ganglion (TG) neurons play a major role in 2MT-induced innate freezing[28]
We showed that exposure to 2MT could induce rapid hypothermia accompanied by elevated tail temperature in wildtype but not Trpa1−/− mice

Summary

Introduction

The neural mechanisms of fear-associated thermoregulation remain unclear. Innate fear odor 2-methyl-2-thiazoline (2MT) elicits 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. Freezing is a typical defensive behavior in preys to avoid detection by predators[13,14,15] Autonomic activities, such as body temperature, heart rate, and blood pressure, can all be regulated as part of the “fight or flight” response under learned and innate fear conditions[16,17]. Exposure to 2MT can evoke rapid reduction in cutaneous and core body temperature accompanying innate fear behaviors in wild-type but not Trpa1−/− mice[30]. Our studies identify the posterior subthalamic nucleus (PSTh) as a major thermoregulatory hub that connects external lateral parabrachial subnucleus (PBel) to nucleus of the solitary tract (NTS) to mediate 2MT-evoked hypothermia and tail vasodilation

Methods

Results

Conclusion