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Boisvert, M. M.

Publications and source records attributed to Boisvert, M. M..

2 recordsLinked to original sources

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 stability. The mechanisms underlying these differing plasticity levels and how they serve to maintain and stabilize the properties of sensory circuits remain largely unclear. By combining a transcriptomic approach with ex vivo electrophysiology and in vivo imaging techniques, we identify that astrocytes release cellular communication network factor 1 (CCN1) to maintain synapse and circuit stability in the visual cortex. By overexpressing CCN1 in critical period astrocytes, we find that it promotes the maturation of inhibitory circuits and limits ocular dominance plasticity. Conversely, by knocking out astrocyte CCN1 in adults, binocular circuits are destabilized. These studies establish CCN1 as a novel astrocyte-secreted factor that stabilizes neuronal circuits. Moreover, they demonstrate that the composition and properties of sensory circuits require ongoing maintenance in adulthood, and that these maintenance cues are provided by astrocytes.

neuroscience↗

Activity-Dependent Modulation of Synapse-Regulating Genes in Astrocytes

Astrocytes regulate the formation and function of neuronal synapses via multiple signals, however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually-evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development are also altered when astrocyte signaling is blunted by diminishing calcium release from astrocyte stores. Single nucleus RNA sequencing identified groups of astrocytic genes regulated by neuronal and astrocyte activity, and a cassette of genes that show layer-specific enrichment. Thus, the development of cortical circuits requires coordinated signaling between astrocytes and neurons, identifying astrocytes as a target to manipulate in neurodevelopmental disorders.

neuroscience↗