GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice

eLife

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[1] Department of Animal Model development, Brain Research Institute, Niigata University, Niigata, Japan;Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan;Department of Neural Regulation,Graduate School of Medicine, Nagoya University, Nagoya, Japan;Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan;Department of Neural Regulation,Graduate School of Medicine, Nagoya University, Nagoya, Japan;CREST, JST, Honcho Kawaguchi, Saitama, Japan;Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan;Department of Neural Regulation,Graduate School of Medicine, Nagoya University, Nagoya, Japan;CREST, JST, Honcho Kawaguchi, Saitama, Japan;Research Fellowship for Young Scientist, Japan Society for the Promotion of Science, Tokyo, Japan;Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan;

关键词: ventral tegmental Area;    non-rapid eye movement sleep;    glutamic acid decarboxylase 67;    chemogenetics;    optogenetics;    fiber photometry;    Mouse;   

DOI  :  10.7554/eLife.44928

来源: publisher

【 摘 要 】

10.7554/eLife.44928.001Sleep/wakefulness cycle is regulated by coordinated interactions between sleep- and wakefulness-regulating neural circuitry. However, the detailed mechanism is far from understood. Here, we found that glutamic acid decarboxylase 67-positive GABAergic neurons in the ventral tegmental area (VTAGad67+) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTAGad67+ project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH). Chemogenetic activation of VTAGad67+ promoted NREM sleep with higher delta power whereas optogenetic inhibition of these induced prompt arousal from NREM sleep, even under highly somnolescent conditions, but not from REM sleep. VTAGad67+ showed the highest activity in NREM sleep and the lowest activity in REM sleep. Moreover, VTAGad67+ directly innervated and inhibited wake-promoting orexin/hypocretin neurons by releasing GABA. As such, optogenetic activation of VTAGad67+ terminals in the LH promoted NREM sleep. Taken together, we revealed that VTAGad67+ play an important role in the regulation of NREM sleep.

【 授权许可】

CC BY