期刊
SCIENCE
卷 341, 期 6149, 页码 1016-1020出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1240729
关键词
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资金
- Chinese 973 Program [2011CBA00400]
- Strategic Priority Research Program (B) of the Chinese Academy of Sciences [XDB02030004]
- Hundreds of Talents Program
- Outstanding Youth Grant
- Shanghai Pujiang Talent Program
- NIH [P41 GM103533, R01 MH067880]
- Simon's Foundation
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.
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