Astrocyte CCN1 stabilizes neural circuits in the adult brain

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. Neural circuits in adult mouse visual cortex are stabilized by astrocytes, which secrete CCN1, resulting in reduced plasticity and increased maturation of multiple cell types.