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

Nat Commun. 2021 May 11;12(1):2648. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature Regulation / physiology
  • Fear / physiology*
  • Fear / psychology
  • Hypothermia / chemically induced
  • Hypothermia / metabolism*
  • Hypothermia / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / metabolism
  • Optogenetics / methods
  • Proto-Oncogene Proteins c-fos / metabolism
  • Solitary Nucleus / metabolism*
  • Subthalamic Nucleus / metabolism*
  • TRPA1 Cation Channel / genetics
  • TRPA1 Cation Channel / metabolism*
  • Thiazoles
  • Vasodilation / physiology

Substances

  • Proto-Oncogene Proteins c-fos
  • TRPA1 Cation Channel
  • Thiazoles
  • Trpa1 protein, mouse
  • 2-methylthiazoline