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GABAergic leptin receptor-expressing neurons in the dorsomedial hypothalamus project to brown adipose tissue-related neurons in the paraventricular nucleus of mice
Autonomic Neuroscience ( IF 2.7 ) Pub Date : 2022-12-14 , DOI: 10.1016/j.autneu.2022.103058
Yanyan Jiang 1 , Kavon Rezai-Zadeh 2 , Lucie D Desmoulins 3 , Heike Muenzberg 2 , Andrei V Derbenev 1 , Andrea Zsombok 1
Affiliation  

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.



中文翻译:

下丘脑背内侧表达 GABA 能瘦素受体的神经元投射到小鼠室旁核中棕色脂肪组织相关的神经元

棕色脂肪组织(BAT)通过非颤抖产热作用促进能量稳态。BAT 受到交感神经系统 (SNS) 的密集支配,前自主神经元的活动调节交感神经的流出。瘦素是一种脂肪细胞激素,通过多个神经元回路改变 BAT 的能量稳态和生热作用;然而,瘦素对下丘脑肩胛间 BAT (iBAT) 相关神经元的细胞作用仍有待确定。在本研究中,我们使用伪狂犬病病毒(PRV)来鉴定下丘脑室旁核(PVN)中与 iBAT 相关的神经元,并检验 iBAT 相关 PVN 神经元受瘦素调节的假设。在瘦素受体报告小鼠 (Lepr:EGFP) 中用 PRV 接种 iBAT 表明,iBAT 相关的 PVN 神经元群体表达 Lepr 受体。我们的电生理学研究结果表明,瘦素的应用导致一些 iBAT 相关 PVN 神经元超极化。瘦素的沐浴应用还调节大多数 iBAT 相关 PVN 神经元的兴奋性和抑制性神经传递。使用通道视紫红质辅助电路映射,我们发现下丘脑背内侧/下丘脑背侧区域(dDMH/DHA)中表达 GABA 能和谷氨酸能 Lepr 的神经元投射到 PVN 神经元;然而,连接的 iBAT 相关 PVN 神经元仅接收来自表达 Lepr 的 dDMH/DHA 神经元的抑制信号。使用通道视紫红质辅助电路映射,我们发现下丘脑背内侧/下丘脑背侧区域(dDMH/DHA)中表达 GABA 能和谷氨酸能 Lepr 的神经元投射到 PVN 神经元;然而,连接的 iBAT 相关 PVN 神经元仅接收来自表达 Lepr 的 dDMH/DHA 神经元的抑制信号。使用通道视紫红质辅助电路映射,我们发现下丘脑背内侧/下丘脑背侧区域(dDMH/DHA)中表达 GABA 能和谷氨酸能 Lepr 的神经元投射到 PVN 神经元;然而,连接的 iBAT 相关 PVN 神经元仅接收来自表达 Lepr 的 dDMH/DHA 神经元的抑制信号。

更新日期:2022-12-19
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