Ca2+ Signals in Astrocytes Facilitate Spread of Epileptiform Activity

Cereb Cortex. 2018 Nov 1;28(11):4036-4048. doi: 10.1093/cercor/bhy196.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / physiology*
  • Calcium Signaling*
  • Epilepsy / chemically induced
  • Epilepsy / physiopathology*
  • Excitatory Amino Acid Agonists / administration & dosage
  • Hippocampus / physiopathology*
  • Inositol 1,4,5-Trisphosphate Receptors / genetics
  • Inositol 1,4,5-Trisphosphate Receptors / physiology
  • Kainic Acid / administration & dosage
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / physiology*
  • Seizures / chemically induced
  • Seizures / physiopathology*


  • Excitatory Amino Acid Agonists
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ip3r2 protein, mouse
  • Kainic Acid