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

Can Liu, Chia-Ying Lee, Greg Asher, Liqin Cao, Yuka Terakoshi, Peng Cao, Reiko Kobayakawa, Ko Kobayakawa, Katsuyasu Sakurai () and Qinghua Liu ()
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Can Liu: Tsinghua University
Chia-Ying Lee: University of Tsukuba
Greg Asher: University of Tsukuba
Liqin Cao: University of Tsukuba
Yuka Terakoshi: University of Tsukuba
Peng Cao: National Institute of Biological Sciences (NIBS)
Reiko Kobayakawa: Kansai Medical University
Ko Kobayakawa: Kansai Medical University
Katsuyasu Sakurai: University of Tsukuba
Qinghua Liu: National Institute of Biological Sciences (NIBS)

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22914-6

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