Excitatory Pathways from the Lateral Habenula Enable Propofol-Induced Sedation

被引：78

作者：

Gelegen, Cigdem ^{[1
]}

Miracca, Giulia ^{[1
]}

Ran, Mingzi Z. ^{[2
]}

Harding, Edward C. ^{[1
]}

Ye, Zhiwen ^{[1
]}

Yu, Xiao ^{[1
]}

Tossell, Kyoko ^{[1
]}

Houston, Catriona M. ^{[1
]}

Yustos, Raquel ^{[1
]}

Hawkins, Edwin D. ^{[1
]}

Vyssotski, Alexei L. ^{[3
]}

Dong, Hailong L. ^{[2
]}

Wisden, William ^{[1
,4
,5
]}

Franks, Nicholas P. ^{[1
,4
,5
]}

机构：

[1] Imperial Coll London, Dept Life Sci, South Kensington SW7 2AZ, England

[2] Xijing Hosp, Dept Anesthesiol & Perioperat Med, Xian 710032, Shaanxi, Peoples R China

[3] Univ Zurich, Inst Neuroinformat, ETH Zurich, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[4] Imperial Coll London, Ctr Excellence Neurotechnol, South Kensington SW7 2AZ, England

[5] Imperial Coll London, UK Dementia Res Inst, South Kensington SW7 2AZ, England

来源：

CURRENT BIOLOGY | 2018年 / 28卷 / 04期

基金：

英国惠康基金; 中国国家自然科学基金; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

VENTRAL TEGMENTAL AREA; GENERAL-ANESTHESIA; NEURONAL-ACTIVITY; DOPAMINE NEURONS; IN-VIVO; SLEEP; ACTIVATION; EXPRESSION; NUCLEUS; MOUSE;

D O I：

10.1016/j.cub.2017.12.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 gluta-matergic, excitatory hub that projects to multiple targets throughout the brain, including GABAergic and aminergic nuclei that control arousal [3-5]. 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.

引用

页码：580 / +

页数：13

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