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

IF 3.2 4区医学 Q2 NEUROSCIENCES

Autonomic Neuroscience-Basic & Clinical Pub Date : 2023-03-01 DOI:10.1016/j.autneu.2022.103058

Yanyan Jiang , Kavon Rezai-Zadeh , Lucie D. Desmoulins , Heike Muenzberg , Andrei V. Derbenev , Andrea Zsombok

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引用次数: 1

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.

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小鼠下丘脑背内侧表达gaba能瘦素受体的神经元向室旁核的棕色脂肪组织相关神经元投射

棕色脂肪组织（BAT）通过非分离产热促进能量稳态。BAT由交感神经系统（SNS）密集支配，自主神经前神经元的活动调节交感神经流出。瘦素，一种脂肪细胞激素，通过几个神经元回路改变BAT的能量稳态和产热；然而，瘦素对下丘脑帽间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）鉴定了下丘脑室旁核（PVN）中的iBAT相关神经元，并验证了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，一群与iBAT相关的PVN神经元表达Lepr受体。我们的电生理学发现，瘦素的应用导致了一些iBAT相关PVN神经元的超极化。瘦素的沐浴应用也调节了对大多数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图，我们发现下丘脑背内侧/下丘脑背侧区域（dDMH/DHA）的GABA能和谷氨酸能Lepr表达神经元投射到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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Autonomic Neuroscience-Basic & Clinical 医学-神经科学

CiteScore

5.80

自引率

7.40%

发文量

审稿时长

66 days

期刊介绍： This is an international journal with broad coverage of all aspects of the autonomic nervous system in man and animals. The main areas of interest include the innervation of blood vessels and viscera, autonomic ganglia, efferent and afferent autonomic pathways, and autonomic nuclei and pathways in the central nervous system. The Editors will consider papers that deal with any aspect of the autonomic nervous system, including structure, physiology, pharmacology, biochemistry, development, evolution, ageing, behavioural aspects, integrative role and influence on emotional and physical states of the body. Interdisciplinary studies will be encouraged. Studies dealing with human pathology will be also welcome.