The Francis Crick Institute
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GABA and glutamate neurons in the VTA regulate sleep and wakefulness

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journal contribution
posted on 2019-12-19, 18:05 authored by 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
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.


Crick (Grant ID: 10055, Grant title: Burdakov FC001055)