期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 219, 期 4, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20210989
关键词
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资金
- Japan Society for the Promotion of Science [KAKENHI 21K19309, 21H04786, 20H05902, 20H05060, 19H04746, 16H06280]
- Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology [JP21gm1310008]
- Core Research for Evolutional Science and Technology [JPMJCR14G2]
- Mitsubishi Science Foundation
- Takeda Science Foundation
- Frontier Brain Science Grant from the University of Yamanashi
- National Research Foundation of Korea - Korean government [NRF-2019R1A2C2086052]
The activation of astrocytes plays a crucial role in brain plasticity and the development of neurological disorders. The presence of mGluR5 in astrocytes, which is absent under normal conditions, is essential for regulating synaptic plasticity and neuronal activity, particularly in the somatosensory cortex.
Activation of astrocytes has a profound effect on brain plasticity and is critical for the pathophysiology of several neurological disorders including neuropathic pain. Here, we show that metabotropic glutamate receptor 5 (mGluR5), which reemerges in astrocytes in a restricted time frame, is essential for these functions. Although mGluR5 is absent in healthy adult astrocytes, it transiently reemerges in astrocytes of the somatosensory cortex (S1). During a limited spatiotemporal time frame, astrocytic mGluR5 drives Ca2+ signals; upregulates multiple synaptogenic molecules such as Thrombospondin-1, Glypican-4, and Nevin; causes excess excitatory synaptogenesis; and produces persistent alteration of S1 neuronal activity, leading to mechanical allodynia. All of these events were abolished by the astrocyte-specific deletion of mGluR5. Astrocytes dynamically control synaptic plasticity by turning on and off a single molecule, mGluR5, which defines subsequent persistent brain functions, especially under pathological conditions.
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