Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression
Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression
复制标题
外侧缰核中的星形胶质细胞 Kir4.1 驱动抑郁症中的神经元爆发
DOI：
10.1038/nature25752
复制
发表时间：
2018-02-15
期刊：
影响因子：
64.8
通讯作者：
Hu, Hailan
中科院分区：
文献类型：
--
作者：
Cui, Yihui;Yang, Yan;Hu, Hailan
外侧缰核（LHb）神经元的爆发活动增强在驱动抑郁样行为中至关重要，但这种增加的原因尚不清楚。在这里，使用高通量定量蛋白质组学筛选，我们表明，星形胶质细胞钾通道（Kir4.1）在抑郁症大鼠模型的LHb上调。Kir4.1在LHb中显示出在紧密包裹神经元索马体的星形胶质细胞膜突起上的独特表达模式。电生理学和建模数据表明，星形胶质细胞上的Kir4.1水平紧密调节膜超极化的程度和LHb神经元的爆发活动的量。星形胶质细胞特异性Kir4.1在LHb中的获得和损失双向调节神经元爆发和抑郁样症状。总之，这些结果表明，在LHb的体周空间的神经胶质-神经元相互作用参与设置神经元放电模式的主要精神疾病的模型。LHb中Kir4.1有可能成为治疗临床抑郁症的靶点。
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.