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Nature. 2018 Feb 14;554(7692):323-327. doi: 10.1038/nature25752.

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

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Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Medicine, Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou 310058, China.
Mental Health Center, School of Medicine, Zhejiang University, Hangzhou 310013, China.
Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, China.
INRIA, Lyon, F-69603, France.
University of Lyon, UMR 5205, CNRS, LIRIS, F-69622, France.


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.

[Indexed for MEDLINE]

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