Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
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.
癫痫发作与星形细胞 Ca2+信号的增加有关，但癫痫发作期间星形细胞-神经元相互作用的精细时空动力学仍然难以捉摸。通过对具有慢性海马窗的清醒固定头部小鼠进行双光子成像，我们证明在海人酸诱导的癫痫发作的初始发作期间，星形细胞 Ca2+信号先于神经元 Ca2+升高。平均而言，星形细胞 Ca2+的升高比 CA1 中的神经元活动早约 8 秒。在随后的癫痫发作发作中，星形细胞和神经元同时被激活。在缺乏 2 型肌醇 1,4,5-三磷酸受体（Itpr2-/-）的小鼠中，初始星形细胞 Ca2+升高被消除。此外，我们发现通过遥测 EEG 监测评估时，Itpr2-/- 小鼠的癫痫样活动比野生型小鼠少 60%。在这两种基因型中，我们还证明扩布性去极化波可能在癫痫发作终止中起作用。我们的发现表明星形细胞 Ca2+信号在癫痫发作发生中起作用。
