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Connected astrocytes help with coordination
Astrocytes are glial cells in the nervous system that are interconnected by gap junctions formed by connexins. Gap junctions form regulated pores that enable the connected cells to function as a unit by rapidly passing cytosolic signals. By analyzing hippocampal slices from mice that were deficient for astroglial connexins, Chever et al. found that interconnected astrocytes coordinated bursts of neuronal activity over large regions, which contributed to the intensity of induced seizures. Indeed, mice with disconnected astrocytes had more frequent, but less severe, chemically induced seizures than normal mice. Thus, intercellular communication between astrocytes enhances the coordination of activity in neuronal networks.
Astrocytes interact with neurons to regulate network activity. Although the gap junction subunits connexin 30 and connexin 43 mediate the formation of extensive astroglial networks that cover large functional neuronal territories, their role in neuronal synchronization remains unknown. Using connexin 30– and connexin 43–deficient mice, we showed that astroglial networks promoted sustained population bursts in hippocampal slices by setting the basal active state of neurons. Astroglial networks limited excessive neuronal depolarization induced by spontaneous synaptic activity, increased neuronal release probability, and favored the recruitment of neurons during bursting, thus promoting the coordinated activation of neuronal networks. In vivo, this sustained neuronal coordination translated into increased severity of acutely evoked epileptiform events and convulsive behavior. These results revealed that connexin-mediated astroglial networks synchronize bursting of neuronal assemblies, which can exacerbate pathological network activity and associated behavior. Our data thus provide molecular and biophysical evidence predicting selective astroglial gap junction inhibitors as anticonvulsive drugs.