A midbrain GABAergic circuit constrains wakefulness in a mouse model of stress

作者全名："Ren, Shuancheng; Zhang, Cai; Yue, Faguo; Tang, Jinxiang; Zhang, Wei; Zheng, Yue; Fang, Yuanyuan; Wang, Na; Song, Zhenbo; Zhang, Zehui; Zhang, Xiaolong; Qin, Han; Wang, Yaling; Xia, Jianxia; Jiang, Chenggang; He, Chao; Luo, Fenlan; Hu, Zhian"

作者地址："[Ren, Shuancheng; Zhang, Cai; Yue, Faguo; Zhang, Wei; Wang, Na; Song, Zhenbo; Zhang, Xiaolong; Wang, Yaling; Xia, Jianxia; He, Chao; Luo, Fenlan; Hu, Zhian] Army Med Univ, Coll Basic Med Sci, Dept Physiol, Chongqing 400038, Peoples R China; [Ren, Shuancheng] No 953 Army Hosp, Shigatse 857000, Tibet Autonomou, Peoples R China; [Yue, Faguo; Tang, Jinxiang] Chongqing Med Univ, Bishan Hosp, Sleep & Psychol Ctr, Chongqing 402760, Peoples R China; [Zheng, Yue] Army Med Univ, Southwest Hosp, Dept Anesthesiol, Chongqing 400038, Peoples R China; [Fang, Yuanyuan] Wuhan Univ, Zhongnan Hosp, Dept Anesthesiol, Wuhan 430071, Peoples R China; [Wang, Na] Chongqing Univ, Coll Bioengn, Chongqing 400044, Peoples R China; [Zhang, Zehui] Jilin Univ, Coll Basic Med Sci, Dept Physiol, Changchun 130021, Peoples R China; [Qin, Han; Hu, Zhian] Chongqing Inst Brain & Intelligence, Guangyang Bay Lab, Chongqing 400064, Peoples R China; [Jiang, Chenggang] Chongqing Med Univ, Women & Childrens Hosp, Chongqing Hlth Ctr Women & Children, Psychol Dept, Chongqing 401147, Peoples R China"

通信作者："Ren, SC; He, C; Luo, FL; Hu, Z (通讯作者)，Army Med Univ, Coll Basic Med Sci, Dept Physiol, Chongqing 400038, Peoples R China.; Ren, SC (通讯作者)，No 953 Army Hosp, Shigatse 857000, Tibet Autonomou, Peoples R China.; Hu, Z (通讯作者)，Chongqing Inst Brain & Intelligence, Guangyang Bay Lab, Chongqing 400064, Peoples R China."

来源：NATURE COMMUNICATIONS

ESI学科分类：　

WOS号：WOS:001195623200021

JCR分区：Q1

影响因子：14.7

年份：2024

卷号：15

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Enhancement of wakefulness is a prerequisite for adaptive behaviors to cope with acute stress, but hyperarousal is associated with impaired behavioral performance. Although the neural circuitries promoting wakefulness in acute stress conditions have been extensively identified, less is known about the circuit mechanisms constraining wakefulness to prevent hyperarousal. Here, we found that chemogenetic or optogenetic activation of GAD2-positive GABAergic neurons in the midbrain dorsal raphe nucleus (DRNGAD2) decreased wakefulness, while inhibition or ablation of these neurons produced an increase in wakefulness along with hyperactivity. Surprisingly, DRNGAD2 neurons were paradoxically wakefulness-active and were further activated by acute stress. Bidirectional manipulations revealed that DRNGAD2 neurons constrained the increase of wakefulness and arousal level in a mouse model of stress. Circuit-specific investigations demonstrated that DRNGAD2 neurons constrained wakefulness via inhibition of the wakefulness-promoting paraventricular thalamus. Therefore, the present study identified a wakefulness-constraining role DRNGAD2 neurons in acute stress conditions. Neural circuit mechanisms underlying prevention of hyperarousal in acute stress conditions are not fully understood. Here authors show GAD2-positive GABAergic neurons in the midbrain dorsal raphe nucleus constrain the increase of wakefulness to prevent hyperarousal in a mouse model of stress."

基金机构："National Natural Science Foundation of China (31921003) China Science and Technology Innovation 2030 for Brain Science and Brain-Inspired Technology (2022ZD0205600) [31921003, 2022ZD0205600, 2021ZD0203400, 82371493, 32022030, 82071492]; National Natural Science Foundation of China"

基金资助正文："We thank all the members from Zhian Hu's lab for critical comments on the paper. This work was supported by the National Natural Science Foundation of China (31921003) to Z.H., National Major Project of China Science and Technology Innovation 2030 for Brain Science and Brain-Inspired Technology (2022ZD0205600) to S.R. and (2021ZD0203400) to Z.H., and National Natural Science Foundation of China (82371493) to S.R., (32022030) to C.H., and (82071492) to F.Y."