Wang Xuxin, Chen Xiaowei, Zhang Zehui, Liu Xiaofeng, Lv Qianqian, Song Meiying, Zhao Danyang, Su Jianjun, Su Yana, Zhao Guoyan, Sun Jianfeng, Lin Weihong, Zhao Hua
Department of Physiology, College of Basic Medical Sciences, Jilin University, Xinmin Street No. 126, Changchun 130021, People's Republic of China.
Department of Rehabilitation Medicine, First Hospital of Jilin University, Changchun 130021, People's Republic of China.
iScience. 2025 Jun 18;28(7):112923. doi: 10.1016/j.isci.2025.112923. eCollection 2025 Jul 18.
The lateral habenula (LHb) is implicated in the regulation of numerous physiological functions, particularly those associated with thermoregulation. It exhibits close anatomical and functional connections with the key brain regions that play a crucial role in regulating body temperature. However, whether the LHb directly contributes to temperature regulation remains unclear. We here report that chemogenetic and optogenetic manipulations of LHb glutamatergic neurons bidirectionally modulated body temperature. When the LHb glutamatergic neurons were impaired, mice exhibited a pronounced intolerance to cold stimuli. Interestingly, we observed differential responses to thermal stimuli between GABAergic neurons in LPO and glutamatergic neurons in LHb. Notably, cold-activated glutamatergic neurons in LHb receive the projections from heat-activated GABAergic neurons in LPO. Using optogenetic techniques to activate the LPO-LHb neural circuit led to significant decreases in body temperature. Collectively, our findings suggest that the glutamatergic neurons in the LHb and the LPO-LHb neural circuit may play a crucial role in temperature regulation.
外侧缰核（LHb）参与多种生理功能的调节，尤其是那些与体温调节相关的功能。它与在调节体温中起关键作用的关键脑区表现出紧密的解剖学和功能联系。然而，LHb是否直接参与体温调节仍不清楚。我们在此报告，对LHb谷氨酸能神经元进行化学遗传学和光遗传学操作可双向调节体温。当LHb谷氨酸能神经元受损时，小鼠对冷刺激表现出明显的不耐受。有趣的是，我们观察到下丘脑外侧区（LPO）的γ-氨基丁酸（GABA）能神经元和LHb的谷氨酸能神经元对热刺激的反应不同。值得注意的是，LHb中冷激活的谷氨酸能神经元接受来自LPO中热激活的GABA能神经元的投射。使用光遗传学技术激活LPO-LHb神经回路会导致体温显著下降。总的来说，我们的研究结果表明，LHb中的谷氨酸能神经元和LPO-LHb神经回路可能在体温调节中起关键作用。
