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Astrocytes play key roles in brain functions through dynamic interactions with neurons. One of their typical features is to express high levels of connexins (Cxs), Cx43 and Cx30, the gap junction (GJ)-forming proteins. Cx30 is involved in basic cognitive processes and shapes synaptic and network activities, as shown by recent studies in transgenic animals. Yet it remains unknown whether astroglial Cx30 expression, localization, and functions are endogenously and dynamically regulated by neuronal activity and could therefore play physiological roles in neurotransmission. We here show that neuronal activity increased hippocampal Cx30 protein levels via a posttranslational mechanism regulating lysosomal degradation. Neuronal activity also increased Cx30 protein levels at membranes and perisynaptic processes, as revealed by superresolution imaging. This translated at the functional level in the activation of Cx30 hemichannels and in Cx30-mediated remodeling of astrocyte morphology independently of GJ biochemical coupling. Altogether, these data show activity-dependent dynamics of Cx30 expression, perisynaptic localization, and functions.

Neuronal Activity Drives Astroglial Connexin 30 in Perisynaptic Processes and Shapes Its Functions