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

来自NERCN

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
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
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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