GABA and glutamate neurons in the VTA regulate sleep and wakefulness
File(s)Yu et al. Nat Neurosci.In press.pdf (14.18 MB)
Accepted version
Author(s)
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.
Date Issued
2019-01
Date Acceptance
2018-11-09
Citation
Nature Neuroscience, 2019, 22 (1), pp.106-119
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
Wellcome Trust
UK DRI Ltd
Wellcome Trust
Wellcome Trust
Identifier
https://www.nature.com/articles/s41593-018-0288-9
Grant Number
107841/Z/15/Z
4050641385
107839/Z/15/Z
107841/Z/15/Z
Subjects
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
Date Publish Online
2018-12-17