Regulation of wakefulness by GABAergic dorsal raphe nucleus-ventral tegmental area pathway

作者：Ping Cai, Fu-Dan Wang, Jing Yao, Wenfeng Wang, Wen-Feng Wang, Yu-Duan Hu, Zhang-Shu Li, Zhang-Shu Li, Zhong-Hua Zhu, Yu-Tong Cai, Zhihui Lin, Wei-Tao Tang, Cong-Wen Zhuang, Wen-Hao Xiao, Yu-Hang Zeng, Shengnan Huang, Zhifei Fu, Wenxiang Wang, Wenxiang Wang, Li Chen · 发表于：SLEEP · 年份：2022 · DOI：10.1093/sleep/zsac235 · 被引用次数：10 · 研究领域：Sleep and Wakefulness Research、Circadian rhythm and melatonin、Sleep and related disorders

The dorsal raphe nucleus (DRN) has previously been proved to be involved in the regulation of the sleep-wake behavior. DRN contains several neuron types, such as 5-HTergic and GABAergic neurons. GABAergic neurons, which are the second largest cell subtype in the DRN, participate in a variety of neurophysiological functions. However, their role in sleep-wake regulation and the underlying neural circuitry remains unclear. Herein, we used fiber photometry and synchronous electroencephalogram (EEG)/electromyography (EMG) recording to demonstrate that DRN GABAergic neurons exhibit high activities during wakefulness and low activities during NREM sleep. Short-term optogenetic activation of DRN GABAergic neurons reduced the latency of NREM-to-wake transition and increased the probability of wakefulness, while long-term optogenetic activation of these neurons significantly increased the amount of wakefulness. Chemogenetic activation of DRN GABAergic neurons increased wakefulness for almost 2 h and maintained long-lasting arousal. In addition, inhibition of DRN GABAergic neurons with chemogenetics caused a reduction in the amount of wakefulness. Finally, similar to the effects of activating the soma of DRN GABAergic neurons, optogenetic stimulation of their terminals in the ventral tegmental area (VTA) induced instant arousal and promoted wakefulness. Taken together, our results illustrated that DRN GABAergic neurons are vital to the induction and maintenance of wakefulness, which pro...