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GABA and glutamate neurons in the VTA regulate sleep and wakefulness.
Nat Neurosci 2019; 22(1):106-119NN

Abstract

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.

Authors+Show Affiliations

Department of Life Sciences, Imperial College London, London, UK.Department of Anesthesiology & Perioperative Medicine, Xijing Hospital, Xi'an, Shanxi, China.Department of Life Sciences, Imperial College London, London, UK.Department of Life Sciences, Imperial College London, London, UK.Department of Life Sciences, Imperial College London, London, UK. The Francis Crick Institute, London, UK.Department of Life Sciences, Imperial College London, London, UK.Department of Life Sciences, Imperial College London, London, UK.Department of Life Sciences, Imperial College London, London, UK.Department of Anesthesiology & Perioperative Medicine, Xijing Hospital, Xi'an, Shanxi, China.Department of Anesthesiology & Perioperative Medicine, Xijing Hospital, Xi'an, Shanxi, China.Department of Anesthesiology & Perioperative Medicine, Xijing Hospital, Xi'an, Shanxi, China.iHuman Institute, ShanghaiTech University, Shanghai, China.Department of Life Sciences, Imperial College London, London, UK.Department of Life Sciences, Imperial College London, London, UK.Institute of Neuroinformatics, University of Zürich/ETH Zürich, Zürich, Switzerland.The Francis Crick Institute, London, UK.Department of Anesthesiology & Perioperative Medicine, Xijing Hospital, Xi'an, Shanxi, China.Department of Anesthesiology & Perioperative Medicine, Xijing Hospital, Xi'an, Shanxi, China. hldong6@hotmail.com.Department of Life Sciences, Imperial College London, London, UK. n.franks@imperial.ac.uk. Centre for Neurotechnology, Imperial College London, London, UK. n.franks@imperial.ac.uk. UK Dementia Research Institute, Imperial College London, London, UK. n.franks@imperial.ac.uk.Department of Life Sciences, Imperial College London, London, UK. w.wisden@imperial.ac.uk. Centre for Neurotechnology, Imperial College London, London, UK. w.wisden@imperial.ac.uk. UK Dementia Research Institute, Imperial College London, London, UK. w.wisden@imperial.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30559475

Citation

Yu, Xiao, et al. "GABA and Glutamate Neurons in the VTA Regulate Sleep and Wakefulness." Nature Neuroscience, vol. 22, no. 1, 2019, pp. 106-119.
Yu X, Li W, Ma Y, et al. GABA and glutamate neurons in the VTA regulate sleep and wakefulness. Nat Neurosci. 2019;22(1):106-119.
Yu, X., Li, W., Ma, Y., Tossell, K., Harris, J. J., Harding, E. C., ... Wisden, W. (2019). GABA and glutamate neurons in the VTA regulate sleep and wakefulness. Nature Neuroscience, 22(1), pp. 106-119. doi:10.1038/s41593-018-0288-9.
Yu X, et al. GABA and Glutamate Neurons in the VTA Regulate Sleep and Wakefulness. Nat Neurosci. 2019;22(1):106-119. PubMed PMID: 30559475.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GABA and glutamate neurons in the VTA regulate sleep and wakefulness. AU - Yu,Xiao, AU - Li,Wen, AU - Ma,Ying, AU - Tossell,Kyoko, AU - Harris,Julia J, AU - Harding,Edward C, AU - Ba,Wei, AU - Miracca,Giulia, AU - Wang,Dan, AU - Li,Long, AU - Guo,Juan, AU - Chen,Ming, AU - Li,Yuqi, AU - Yustos,Raquel, AU - Vyssotski,Alexei L, AU - Burdakov,Denis, AU - Yang,Qianzi, AU - Dong,Hailong, AU - Franks,Nicholas P, AU - Wisden,William, Y1 - 2018/12/17/ PY - 2018/07/16/received PY - 2018/11/09/accepted PY - 2018/12/19/entrez PY - 2018/12/19/pubmed PY - 2019/5/22/medline SP - 106 EP - 119 JF - Nature neuroscience JO - Nat. Neurosci. VL - 22 IS - 1 N2 - 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. SN - 1546-1726 UR - https://www.unboundmedicine.com/medline/citation/30559475/GABA_and_glutamate_neurons_in_the_VTA_regulate_sleep_and_wakefulness_ L2 - http://dx.doi.org/10.1038/s41593-018-0288-9 DB - PRIME DP - Unbound Medicine ER -