Altmetric

Excitatory pathways from the lateral habenula enable propofol-induced sedation

File Description SizeFormat 
1-s2.0-S0960982217316834-main.pdfPublished version2.84 MBAdobe PDFView/Open
Title: Excitatory pathways from the lateral habenula enable propofol-induced sedation
Authors: Gelegen, C
Miracca, G
Ran, M
Harding, E
Ye, Z
Yu, X
Tossell, K
Houston, C
Yustos, R
Hawkins, E
Vyssotski, A
Dong, H
Wisden, W
Franks, NP
Item 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.
Issue Date: 1-Feb-2018
Date of Acceptance: 21-Dec-2017
URI: http://hdl.handle.net/10044/1/55612
DOI: https://dx.doi.org/10.1016/j.cub.2017.12.050
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/ ).
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Wellcome Trust
UK DRI Ltd
Funder's Grant Number: 107839/Z/15/Z
107841/Z/15/Z
107841/Z/15/Z
N/A
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
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
06 Biological Sciences
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Developmental Biology
Publication Status: Published
Appears in Collections:Faculty of Natural Sciences



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons