A hypothalamic circuit that controls body temperature
A hypothalamic circuit that controls body temperature
复制标题
控制体温的下丘脑回路。
DOI：
10.1073/pnas.1616255114
复制
发表时间：
2017-02-21
影响因子：
11.1
通讯作者：
Shen, Wei L.
中科院分区：
文献类型：
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作者：
Zhao, Zheng-Dong;Yang, Wen Z.;Shen, Wei L.
体温的稳态控制对于哺乳动物的生存至关重要，并且已知部分由下丘脑中的温度敏感神经元调节。然而，具体的神经通路和相应的神经群体尚未完全阐明。为了识别这些通路，我们使用 cFos 染色来识别由热挑战激活的神经元，并发现外侧视前核 (vLPO) 腹侧部分和下丘脑背内侧 (DMD) 背侧部分内的神经元子集中有诱导表达。使用光遗传学激活 vLPO 中的 GABA 能神经元可降低体温，同时减少体力活动。这些神经元的光遗传学抑制导致发烧水平的高热。这些 GABA 能神经元从 vLPO 投射到 DMD，并且 DMD 中神经末梢的光遗传学刺激也降低了体温和活动。电生理记录显示，vLPO GABA 能神经元抑制 DMD 神经元的神经活动，钙瞬变纤维光度测定显示 DMD 神经元被寒冷激活。因此，使用专门由设计药物（DREADD）或光遗传学激活的设计受体激活DMD神经元会增加体温，同时能量消耗和活动也会大幅增加。最后，DMD 神经元的光遗传学抑制引发体温过低，类似于刺激 vLPO 中的 GABA 能神经元。因此，vLPO GABA能神经元抑制DMD神经元的生热效应。总的来说，我们的数据识别出 vLPO。 DMD 神经通路可降低核心温度以应对热挑战，我们表明 DMD 的输出可以诱导活动诱导的生热作用。
The homeostatic control of body temperature is essential for survival in mammals and is known to be regulated in part by temperature-sensitive neurons in the hypothalamus. However, the specific neural pathways and corresponding neural populations have not been fully elucidated. To identify these pathways, we used cFos staining to identify neurons that are activated by a thermal challenge and found induced expression in subsets of neurons within the ventral part of the lateral preoptic nucleus (vLPO) and the dorsal part of the dorsomedial hypothalamus (DMD). Activation of GABAergic neurons in the vLPO using optogenetics reduced body temperature, along with a decrease in physical activity. Optogenetic inhibition of these neurons resulted in fever-level hyperthermia. These GABAergic neurons project from the vLPO to the DMD and optogenetic stimulation of the nerve terminals in the DMD also reduced body temperature and activity. Electrophysiological recording revealed that the vLPO GABAergic neurons suppressed neural activity in DMD neurons, and fiber photometry of calcium transients revealed that DMD neurons were activated by cold. Accordingly, activation of DMD neurons using designer receptors exclusively activated by designer drugs (DREADDs) or optogenetics increased body temperature with a strong increase in energy expenditure and activity. Finally, optogenetic inhibition of DMD neurons triggered hypothermia, similar to stimulation of the GABAergic neurons in the vLPO. Thus, vLPO GABAergic neurons suppressed the thermogenic effect of DMD neurons. In aggregate, our data identify vLPO. DMD neural pathways that reduce core temperature in response to a thermal challenge, and we show that outputs from the DMD can induce activity-induced thermogenesis.