美国索尔克生物研究所Nicola J. Allen小组的一项最新研究开发出了星形胶质细胞CCN1稳定成人大脑的神经回路。2025年12月17日，国际知名学术期刊《自然》发表了这一成果。

在这里，该课题组采取全面的方法来解决这些问题，并建立星形胶质细胞作为电路稳定性的关键协调者。结合转录组学方法与体外电生理学和体内成像，研究人员发现星形胶质细胞释放CCN1维持成人视觉皮层突触和回路的稳定性。星形胶质细胞在关键时期过表达CCN1可促进抑制性神经元的成熟，限制眼优势可塑性，促进少突胶质细胞分化成熟。相反，在成人中敲除星形胶质细胞CCN1会破坏双眼回路的稳定性并减少髓鞘形成。这证实了CCN1是星形胶质细胞分泌的因子，通过协调多种细胞类型的成熟状态来稳定神经元回路，并证明了感觉回路的组成和特性在成年期需要持续的维护，而这些维护线索是由星形胶质细胞提供的。

据了解，大脑中许多区域的神经回路是由经验完善的。在关键时期，即回路完善和成熟的时期，感觉回路在较年轻的年龄支持较高的可塑性，而在成年期限制可塑性以保持回路的稳定性。星形胶质细胞是一种胶质细胞亚型，它们如何维持这些不同的可塑性水平，以及它们是否稳定了成年期感觉回路的特性，这些在很大程度上仍不清楚。

附：英文原文

Title: Astrocyte CCN1 stabilizes neural circuits in the adult brain

Author: Sancho, Laura, Boisvert, Matthew M., Eddy, Trinity, Burgado, Jillybeth, Contreras, Minerva, Labarta-Bajo, Lara, Wang, Ellen, Tatsumi, Lisa, Allen, Nicola J.

Issue&Volume: 2025-12-17

Abstract: Neural circuits in many brain regions are refined by experience. Sensory circuits support higher plasticity at younger ages during critical periods—times of circuit refinement and maturation—and limit plasticity in adulthood for circuit stability1,2. How astrocytes, a glial subtype, maintain these differing plasticity levels, and whether they stabilize the properties of sensory circuits in adulthood, remain largely unclear. Here we take a comprehensive approach to address these questions and establish astrocytes as key orchestrators of circuit stability. Combining a transcriptomic approach with ex vivo electrophysiology and in vivo imaging, we identify that astrocytes release CCN1 (refs. 3,4) to maintain synapse and circuit stability in the adult visual cortex. Overexpressing CCN1 in astrocytes during the critical period promotes the maturation of inhibitory neurons, limits ocular dominance plasticity and promotes oligodendrocyte differentiation and maturation. Conversely, knocking out astrocyte CCN1 in adults destabilizes binocular circuits and reduces myelination. This establishes CCN1 as an astrocyte-secreted factor that stabilizes neuronal circuits by coordinating the maturation state of multiple cell types, and demonstrates that the composition and properties of sensory circuits require ongoing maintenance in adulthood, and that these maintenance cues are provided by astrocytes.

DOI: 10.1038/s41586-025-09770-w

Source: https://www.nature.com/articles/s41586-025-09770-w