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星形胶质细胞关闭了小鼠视觉可塑性的关键期。

Astrocytes close the mouse critical period for visual plasticity.

机构信息

Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University, Paris, France.

Doctoral School N°568, Paris Saclay University, PSL Research University, Le Kremlin Bicetre, France.

出版信息

Science. 2021 Jul 2;373(6550):77-81. doi: 10.1126/science.abf5273.

Abstract

Brain postnatal development is characterized by critical periods of experience-dependent remodeling of neuronal circuits. Failure to end these periods results in neurodevelopmental disorders. The cellular processes defining critical-period timing remain unclear. Here, we show that in the mouse visual cortex, astrocytes control critical-period closure. We uncover the underlying pathway, which involves astrocytic regulation of the extracellular matrix, allowing interneuron maturation. Unconventional astrocyte connexin signaling hinders expression of extracellular matrix-degrading enzyme matrix metalloproteinase 9 (MMP9) through RhoA-guanosine triphosphatase activation. Thus, astrocytes not only influence the activity of single synapses but also are key elements in the experience-dependent wiring of brain circuits.

摘要

大脑的出生后发育以神经元回路的经验依赖性重塑的关键期为特征。如果不能结束这些时期,就会导致神经发育障碍。定义关键期时间的细胞过程仍不清楚。在这里,我们表明在小鼠视觉皮层中,星形胶质细胞控制关键期的关闭。我们揭示了潜在的途径,其中涉及星形胶质细胞对细胞外基质的调节,从而允许中间神经元成熟。非典型星形胶质细胞连接蛋白信号通过 RhoA-鸟嘌呤三磷酸酶激活来抑制细胞外基质降解酶基质金属蛋白酶 9(MMP9)的表达。因此,星形胶质细胞不仅影响单个突触的活性,而且还是大脑回路的经验依赖性布线中的关键要素。

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