Neurons in ventral tegmental area tonically inhibit sympathetic outflow to brown adipose tissue: possible mediation of thermogenic signals from lateral habenula

Mariana Brizuela, Steven J Swoap, James Ang, William W Blessing, Youichirou Ootsuka

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The lateral habenula (LHb), a nucleus involved in the response to salient, especially adverse, environmental events, is implicated in brown adipose tissue (BAT) thermogenesis caused by these events. LHb-elicited thermogenesis involves a neural pathway to the lower brain stem sympathetic control center in the medullary raphé. There are no direct connections from the LHb to the medullary raphé. LHb-mediated behavioral responses involve inhibitory control over the dopamine neurons in the ventral tegmental area (VTA), mediated via an excitatory drive from the LHb to GABAergic neurons in the tail of the VTA. We hypothesized that inhibition of the VTA is also involved in LHb-mediated BAT thermogenesis. To test this hypothesis, inhibition of neurons in the VTA with muscimol increased BAT sympathetic nerve discharge by 22.0 ±; 9.2 dBµV (n = 24, P < 0.0001) and BAT temperature by 1.2 ± 0.1°C (P < 0.001). This response was abolished by inhibition of the medullary raphé neurons with muscimol. BAT thermogenesis initiated with focal injections of bicuculline in the LHb was reversed by subsequent blockade of GABAA receptors in the VTA with bicuculline. These results suggest that, at least in anesthetized rats, neurons in the VTA tonically inhibit BAT thermogenesis via a link, presently unknown, to the medullary raphé. Removal of this VTA-initiated inhibition is an important mechanism whereby LHb neurons activate BAT thermogenesis.

Original languageEnglish
Pages (from-to)R6-R12
JournalAmerican Journal of Physiology-Regulatory Integrative and Comparative Physiology
Volume316
Issue number1
Early online date8 Nov 2018
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • ventral tegmental area
  • thermogenic signals
  • neutrons
  • brown adipose tissue
  • Lateral habenula
  • VTA
  • Dopamine
  • Thermogenesis
  • BAT
  • LHb

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