Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression
推荐理由
证明了LHb细胞周围空间的神经胶质-神经元相互作用参与了神经元放电模式的设置并提出LHb中的Kir4.1有潜力作为治疗抑郁症的靶点。
文章简介 | |
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期刊 | NATURE |
发表年份 | 2018 |
DOI | 10.1038/nature25752 |
类型 | 研究性工作 |
领域 | 抑郁症的病理机制 |
引用量 | 408 |
推荐信息 | |
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推荐人 | 温小妍 |
审核 | 胡春华 |
推荐小组 | 抑郁小组 |
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.
细分领域
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