Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression

被引：458

作者：

Cui, Yihui ^{[1
,2
]}

Yang, Yan ^{[1
,2
]}

Ni, Zheyi ^{[1
]}

Dong, Yiyan ^{[1
]}

Cai, Guohong ^{[3
]}

Foncelle, Alexandre ^{[4
,5
]}

Ma, Shuangshuang ^{[1
]}

Sang, Kangning ^{[1
]}

Tang, Siyang ^{[1
]}

Li, Yuezhou ^{[1
]}

Shen, Ying ^{[1
]}

Berry, Hugues ^{[4
,5
]}

Wu, Shengxi ^{[3
]}

Hu, Hailan ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Interdisciplinary Inst Neurosci & Technol, Qiushi Acad Adv Studies,Ctr Neurosci, Key Lab Med Neurobiol,Minist Hlth China,Sch Med, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Univ, Sch Med, Mental Hlth Ctr, Hangzhou 310013, Zhejiang, Peoples R China

[3] Fourth Mil Med Univ, Sch Basic Med, Dept Neurobiol, Xian 710032, Shaanxi, Peoples R China

[4] INRIA, F-69603 Lyon, France

[5] Univ Lyon, CNRS, UMR 5205, LIRIS, F-69622 Lyon, France

来源：

NATURE | 2018年 / 554卷 / 7692期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

RECTIFYING POTASSIUM CHANNELS; ASTROCYTES; DYSFUNCTION; INHIBITION; PHENOTYPES; NETWORKS; DISEASE; REWARD; INPUT; MODEL;

D O I：

10.1038/nature25752

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Enhanced bursting activity of neurons in the lateral habenula (LHb) is essential in driving depression-like behaviours, but the cause of this increase has been unknown. Here, using a high-throughput quantitative proteomic screen, we show that an astroglial potassium channel (Kir4.1) is upregulated in the LHb in rat models of depression. Kir4.1 in the LHb shows a distinct pattern of expression on astrocytic membrane processes that wrap tightly around the neuronal soma. Electrophysiology and modelling data show that the level of Kir4.1 on astrocytes tightly regulates the degree of membrane hyperpolarization and the amount of bursting activity of LHb neurons. Astrocyte-specific gain and loss of Kir4.1 in the LHb bidirectionally regulates neuronal bursting and depression-like symptoms. Together, these results show that a glia-neuron interaction at the perisomatic space of LHb is involved in setting the neuronal firing mode in models of a major psychiatric disease. Kir4.1 in the LHb might have potential as a target for treating clinical depression.

引用

页码：323 / +

页数：18

共 37 条

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