Astrocytes stabilize circuits in the adult mouse brain using the protein CCN1, which could be targeted to restore plasticity in injury, disorder, or disease

Good news! Amazing stuff! Could be a breakthrough!

"... This flexibility is called neuroplasticity, and our ability to learn, make new memories, and recover from injury all depend on it. ... team have now discovered a molecule that is critical for stabilizing brain circuits in adulthood: a protein called CCN1 secreted by star-shaped cells called astrocytes. The CCN1 pathway could now be a prime target for new therapeutics designed to support learning and plasticity in conditions like Alzheimer’s disease, depression, or PTSD, or to promote neural repair after injury or stroke."

From the 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 stability. 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 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."

🧠 SALK DECEMBER NEWS 🧠

How do brains stay stable, and when might a dose of flexibility be helpful?

Astrocyte CCN1 stabilizes neural circuits in the adult brain (open access)

Fig. 1: Identifying CCN1 as an astrocyte pro-stability factor in the mouse visual cortex.