Regulation of Energy Expenditure by Brainstem GABA Neurons

Homeostatic control of core body temperature is essential for survival. Temperature is sensed by specific neurons, in turn eliciting both behavioral (i.e., locomotion) and physiologic (i.e., thermogenesis, vasodilatation) responses. Here, we report that a population of GABAergic (Vgat-expressing) neurons in the dorsolateral portion of the dorsal raphe nucleus (DRN), hereafter DRNVgat neurons, are activated by ambient heat and bidirectionally regulate energy expenditure through changes in both thermogenesis and locomotion. We find that DRNVgat neurons innervate brown fat via a descending projection to the raphe pallidus (RPa). These neurons also densely innervate ascending targets implicated in the central regulation of energy expenditure, including the hypothalamus and extended amygdala. Optogenetic stimulation of different projection targets reveals that DRNVgat neurons are capable of regulating thermogenesis through both a “direct” descending pathway through the RPa and multiple “indirect” ascending pathways. This work establishes a key regulatory role for DRNVgat neurons in controlling energy expenditure. [Display omitted] •Ambient warmth activates DRNVgat neurons•DRNVgat neurons regulate energy expenditure through locomotion and thermogenesis•DRNVgat neurons exhibit vast projections and polysynaptically innervate brown fat•DRNVgat projections differentially regulate food intake and energy expenditure A population of heat-activated GABAergic neurons in the dorsal raphe nucleus (DRN) regulate energy expenditure through changes in thermogenesis and locomotion.