GABAergic leptin receptor-expressing neurons in the dorsomedial hypothalamus project to brown adipose tissue-related neurons in the paraventricular nucleus of mice

Abstract

Brown adipose tissue (BAT) contributes to energy homeostasis via nonshivering thermogenesis. The BAT is densely innervated by the sympathetic nervous system (SNS) and activity of pre-autonomic neurons modulates the sympathetic outflow. Leptin, an adipocyte hormone, alters energy homeostasis and thermogenesis of BAT via several neuronal circuits; however, the cellular effects of leptin on interscapular BAT (iBAT)-related neurons in the hypothalamus remain to be determined. In this study, we used pseudorabies virus (PRV) to identify iBAT-related neurons in the paraventricular nucleus (PVN) of the hypothalamus and test the hypothesis that iBAT-related PVN neurons are modulated by leptin. Inoculation of iBAT with PRV in leptin receptor reporter mice (Lepr:EGFP) demonstrated that a population of iBAT-related PVN neurons expresses Lepr receptors. Our electrophysiological findings revealed that leptin application caused hyperpolarization in some of iBAT-related PVN neurons. Bath application of leptin also modulated excitatory and inhibitory neurotransmission to most of iBAT-related PVN neurons. Using channel rhodopsin assisted circuit mapping we found that GABAergic and glutamatergic Lepr-expressing neurons in the dorsomedial hypothalamus/dorsal hypothalamic area (dDMH/DHA) project to PVN neurons; however, connected iBAT-related PVN neurons receive exclusively inhibitory signals from Lepr-expressing dDMH/DHA neurons.