βCaMKII in Lateral Habenula Mediates Core Symptoms of Depression

被引：394

作者：

Li, Kun ^{[1
,2
,3
]}

Zhou, Tao ^{[1
,2
,3
]}

Liao, Lujian ^{[4
]}

Yang, Zhongfei ^{[1
,2
]}

Wong, Catherine ^{[4
]}

Henn, Fritz ^{[5
]}

Malinow, Roberto ^{[6
]}

Yates, John R., III ^{[4
]}

Hu, Hailan ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Neurosci, Shanghai 200031, Peoples R China

[3] Univ Chinese Acad Sci, Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China

[4] Scripps Res Inst, Dept Mol & Cellular Neurobiol, La Jolla, CA 92037 USA

[5] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[6] Univ Calif San Diego, La Jolla, CA 92093 USA

来源：

SCIENCE | 2013年 / 341卷 / 6149期

关键词：

DEPENDENT-PROTEIN-KINASE; VENTRAL TEGMENTAL AREA; MAJOR DEPRESSION; BASAL GANGLIA; STRESS; NEURONS; MODEL; NEUROTOXICITY; HIPPOCAMPUS; ACTIVATION;

D O I：

10.1126/science.1240729

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The lateral habenula (LHb) has recently emerged as a key brain region in the pathophysiology of depression. However, the molecular mechanism by which LHb becomes hyperactive in depression remains unknown. Through a quantitative proteomic screen, we found that expression of the beta form of calcium/calmodulin-dependent protein kinase type II (beta CaMKII) was significantly up-regulated in the LHb of animal models of depression and down-regulated by antidepressants. Increasing beta-, but not alpha-, CaMKII in the LHb strongly enhanced the synaptic efficacy and spike output of LHb neurons and was sufficient to produce profound depressive symptoms, including anhedonia and behavioral despair. Down-regulation of beta CaMKII levels, blocking its activity or its target molecule the glutamate receptor GluR1 reversed the depressive symptoms. These results identify beta CaMKII as a powerful regulator of LHb neuron function and a key molecular determinant of depression.

引用

页码：1016 / 1020

页数：5

共 39 条

[1]

Molecular characterization of the subnuclei in rat habenula [J].