Excitatory pathways from the lateral habenula enable propofol-induced sedation
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The lateral habenula has been widely studied for its contribution in generating reward-related behaviors [1 ; 2]. We have found that this nucleus plays an unexpected role in the sedative actions of the general anesthetic propofol. The lateral habenula is a glutamatergic, excitatory hub that projects to multiple targets throughout the brain, including GABAergic and aminergic nuclei that control arousal [3; 4 ; 5]. When glutamate release from the lateral habenula in mice was genetically blocked, the ability of propofol to induce sedation was greatly diminished. In addition to this reduced sensitivity to propofol, blocking output from the lateral habenula caused natural non-rapid eye movement (NREM) sleep to become highly fragmented, especially during the rest (“lights on”) period. This fragmentation was largely reversed by the dual orexinergic antagonist almorexant. We conclude that the glutamatergic output from the lateral habenula is permissive for the sedative actions of propofol and is also necessary for the consolidation of natural sleep.
Date Issued
2018-02-19
Date Acceptance
2017-12-21
Citation
Current Biology, 2018, 28 (4), pp.580-587.e5
ISSN
1879-0445
Publisher
Elsevier
Start Page
580
End Page
587.e5
Journal / Book Title
Current Biology
Volume
28
Issue
4
Copyright Statement
ª
2018 The Authors. Published by Elsevier Ltd.
This is an open access article under the CC BY license (
http://creativecommons.org/licenses/by/4.0/
).
2018 The Authors. Published by Elsevier Ltd.
This is an open access article under the CC BY license (
http://creativecommons.org/licenses/by/4.0/
).
License URL
Sponsor
Wellcome Trust
Wellcome Trust
Wellcome Trust
UK DRI Ltd
Medical Research Council (MRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Identifier
https://www.sciencedirect.com/science/article/pii/S0960982217316834?via%3Dihub
Grant Number
107839/Z/15/Z
107841/Z/15/Z
107841/Z/15/Z
4050641385
G0901892
BB/K018159/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Cell Biology
Life Sciences & Biomedicine - Other Topics
VENTRAL TEGMENTAL AREA
GENERAL-ANESTHESIA
NEURONAL-ACTIVITY
DOPAMINE NEURONS
IN-VIVO
SLEEP
ACTIVATION
EXPRESSION
NUCLEUS
MOUSE
anesthetic mechanisms
neuronal circuitry
orexin
sedative
sleep architecture
tetanus toxin
Anesthetics, Intravenous
Animals
Glutamic Acid
HEK293 Cells
Habenula
Humans
Hypnotics and Sedatives
Male
Mice
Neural Pathways
Propofol
Habenula
Neural Pathways
Animals
Humans
Mice
Propofol
Glutamic Acid
Anesthetics, Intravenous
Hypnotics and Sedatives
Male
HEK293 Cells
06 Biological Sciences
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Developmental Biology
Publication Status
Published
Date Publish Online
2018-02-01