Direct projection from the dorsomedial hypothalamus to the rostral medullary raphe drives brown adipose tissue thermogenesis

Abstract

In the central regulation of thermogenesis in brown adipose tissue (BAT), sympathetic premotor neurons in the rostral medullary raphe (rMR) play a pivotal role by integrating inputs from upper brain sites and by providing an output to the spinal cord. One of the candidate brain sites that provide direct excitatory inputs to these premotor neurons is the dorsomedial hypothalamus (DMH). Using an optogenetic technique, we examined the functional role of the DMH‐rMR projection in the efferent mechanism driving BAT thermogenesis. Virus‐mediated delivery of channelrhodopsin‐2 (ChR2) gene into rat DMH resulted in localization of ChR2 proteins not only in DMH neurons but also in their axon terminals in the rMR. In vivo photostimulation of ChR2‐containing axons in the rMR elicited increases in BAT thermogenesis, blood pressure and heart rate. Photostimulation of ChR2‐expressing cell bodies in the DMH also elicited similar physiological responses, which were eliminated by antagonizing glutamate receptors in the rMR. The responses to photostimulation of ChR2‐containing terminals in the rMR were inhibited by warming the preoptic area (POA). These results indicate that the DMH‐rMR projection provides a glutamatergic input to sympathetic premotor neurons to drive thermogenic and cardiovascular responses and that this activation of sympathetic premotor neurons is influenced by thermal information from the POA.