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GABA and glutamate neurons in the VTA regulate sleep and wakefulness


Authors: Xiao Yu, Wen Li, Ying Ma, Kyoko Tossell, Julia J. Harris, Edward C. Harding, Wei Ba, Giulia Miracca, Dan Wang, Long Li, Juan Guo, Ming Chen, Yuqi Li, Raquel Yustos, Alexei L. Vyssotski, Denis Burdakov, Qianzi Yang, Hailong Dong, Nicholas P. Franks, William Wisden
Publication: Nature Neuroscience
Date: December 17, 2018
Link to article: https://www.nature.com/articles/s41593-018-0288-9?__hssc=91116613.68.1608871335…


We screened for novel circuits in the mouse brain that promote wakefulness. Chemogenetic activation experiments and electroencephalogram recordings pointed to glutamatergic/nitrergic (NOS1) and GABAergic neurons in the ventral tegmental area (VTA). Activating glutamatergic/NOS1 neurons, which were wake- and rapid eye movement (REM) sleep-active, produced wakefulness through projections to the nucleus accumbens and the lateral hypothalamus. Lesioning the glutamate cells impaired the consolidation of wakefulness. By contrast, activation of GABAergic VTA neurons elicited long-lasting non-rapid-eye-movement-like sleep resembling sedation. Lesioning these neurons produced an increase in wakefulness that persisted for at least 4 months. Surprisingly, these VTA GABAergic neurons were wake- and REM sleep-active. We suggest that GABAergic VTA neurons may limit wakefulness by inhibiting the arousal-promoting VTA glutamatergic and/or dopaminergic neurons and through projections to the lateral hypothalamus. Thus, in addition to its contribution to goal- and reward-directed behaviors, the VTA has a role in regulating sleep and wakefulness.

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