Ca2+ Signals in Astrocytes Facilitate Spread of Epileptiform Activity

Abstract

Epileptic seizures are associated with increased astrocytic Ca²⁺ signaling, but the fine spatiotemporal kinetics of the ictal astrocyte–neuron interplay remains elusive. By using 2-photon imaging of awake head-fixed mice with chronic hippocampal windows we demonstrate that astrocytic Ca²⁺ signals precede neuronal Ca²⁺ elevations during the initial bout of kainate-induced seizures. On average, astrocytic Ca²⁺ elevations preceded neuronal activity in CA1 by about 8 s. In subsequent bouts of epileptic seizures, astrocytes and neurons were activated simultaneously. The initial astrocytic Ca²⁺ elevation was abolished in mice lacking the type 2 inositol-1,4,5-trisphosphate-receptor (Itpr2^−/−). Furthermore, we found that Itpr2^−/− mice exhibited 60% less epileptiform activity compared with wild-type mice when assessed by telemetric EEG monitoring. In both genotypes we also demonstrate that spreading depression waves may play a part in seizure termination. Our findings imply a role for astrocytic Ca²⁺ signals in ictogenesis.

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