Glia-neuron interactions underlie state transitions to generalized seizures

SUMMARY Brain activity and connectivity alter drastically during epileptic seizures. Throughout this transition, brain networks shift from a balanced resting state to a hyperactive and hypersynchronous state, spreading across the brain. It is, however, less clear which mechanisms underlie these state transitions. By studying neuronal and glial activity across the zebrafish brain, we observed striking differences between these networks. During the preictal period, neurons displayed a small increase in synchronous activity only locally, while the entire glial network was highly active and strongly synchronized across large distances. We observed that the transition from a preictal state to a generalized seizure leads to an abrupt increase in neuronal activity and connectivity, which is accompanied by a strong functional coupling between glial and neuronal networks. Optogenetic activation of glia induced strong and transient burst of neuronal activity, emphasizing a potential role for glia-neuron connections in the generation of epileptic seizures.