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GABA and glutamate neurons in the VTA regulate sleep and wakefulness

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Yu et al. Nat Neurosci.In press.pdfAccepted version14.52 MBAdobe PDFView/Open
Title: GABA and glutamate neurons in the VTA regulate sleep and wakefulness
Authors: Yu, X
Li, W
Ma, Y
Tossell, K
Harris, J
Harding, E
Ba, W
Miracca, G
Wang, D
Li, L
Guo, J
Chen, M
Li, Y
Yustos, R
Vyssotski, A
Burdakov, D
Yang, Q
Dong, H
Franks, N
Wisden, W
Item Type: Journal Article
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.
Issue Date: Jan-2019
Date of Acceptance: 9-Nov-2018
URI: http://hdl.handle.net/10044/1/65390
DOI: 10.1038/s41593-018-0288-9
ISSN: 1097-6256
Publisher: Nature Publishing Group
Start Page: 106
End Page: 119
Journal / Book Title: Nature Neuroscience
Volume: 22
Issue: 1
Copyright Statement: © 2018 The Author(s), under exclusive licence to Springer Nature America, Inc.
Sponsor/Funder: Wellcome Trust
UK DRI Ltd
Wellcome Trust
Wellcome Trust
Funder's Grant Number: 107841/Z/15/Z
4050641385
107839/Z/15/Z
107841/Z/15/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Neurosciences
Neurosciences & Neurology
VENTRAL TEGMENTAL AREA
DOPAMINE NEURONS
GABAERGIC NEURONS
LATERAL HYPOTHALAMUS
LEPTIN ACTION
ACTIVATION
CIRCUIT
REWARD
DRIVE
PROTEINS
Animals
Dopaminergic Neurons
GABAergic Neurons
Glutamic Acid
Mice
Neurons
Nitric Oxide Synthase Type I
Sleep
Sleep, REM
Ventral Tegmental Area
Wakefulness
Ventral Tegmental Area
Neurons
Animals
Mice
Glutamic Acid
Wakefulness
Sleep
Sleep, REM
Nitric Oxide Synthase Type I
Dopaminergic Neurons
GABAergic Neurons
1109 Neurosciences
1701 Psychology
1702 Cognitive Sciences
Neurology & Neurosurgery
Publication Status: Published
Online Publication Date: 2018-12-17
Appears in Collections:Faculty of Natural Sciences