期刊
NATURE NEUROSCIENCE
卷 22, 期 1, 页码 106-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-018-0288-9
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资金
- Wellcome Trust [104931/Z/14/Z, 107839/Z/15/Z, 107841/Z/15/Z, FC001055]
- UK Dementia Research Institute
- Funds for International Cooperation and Exchange of the National Natural Science Foundation of China [81620108012]
- China Scholarship Council
- Rubicon Fellowship from the Netherlands Organization for Scientific Research [019.161LW. 010]
- Imperial College Junior Research Fellowship
- Francis Crick Institute from Cancer Research UK [FC001055]
- Medical Research Council [FC001055]
- BBSRC [BB/L015129/1]
- Imperial College Schrodinger Scholarship
- Wellcome Trust [107839/Z/15/Z, 107841/Z/15/Z] Funding Source: Wellcome Trust
- BBSRC [BB/L015129/1] Funding Source: UKRI
- MRC [UKDRI-5004] Funding Source: UKRI
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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