First Author | Heuser K | Year | 2018 |
Journal | Cereb Cortex | Volume | 28 |
Issue | 11 | Pages | 4036-4048 |
PubMed ID | 30169757 | Mgi Jnum | J:281686 |
Mgi Id | MGI:6377642 | Doi | 10.1093/cercor/bhy196 |
Citation | Heuser K, et al. (2018) Ca2+ Signals in Astrocytes Facilitate Spread of Epileptiform Activity. Cereb Cortex 28(11):4036-4048 |
abstractText | 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. |