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