Glial Calcium Waves are Triggered by Seizure Activity and Not Essential for Initiating Ictal Onset or Neurovascular Coupling
Glial Calcium Waves are Triggered by Seizure Activity and Not Essential for Initiating Ictal Onset or Neurovascular Coupling
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DOI：
10.1093/cercor/bhx072
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发表时间：
2017-06-01
期刊：
影响因子：
3.7
通讯作者：
Schwartz, Theodore H.
中科院分区：
文献类型：
--
作者：
Baird-Daniel, Eliza;Daniel, Andy G. S.;Schwartz, Theodore H.
据推测，神经胶质细胞在改变神经元活动、介导神经血管耦合和癫痫发作中发挥着关键作用。我们通过局灶性新皮质癫痫体内大鼠模型中钙的广域多细胞和 2 光子单细胞成像以及脑血容量的内在信号成像，研究了神经胶质细胞在癫痫发生和神经血管耦合中的作用。发作事件触发缓慢传播的神经胶质钙波，该波在神经元和血流动力学发作后明显延迟。神经胶质钙波表现出典型的传播，在癫痫发作抵消之前终止，并传播到比神经和血管信号传播区域大 60% 的区域。用氟乙酸盐完全阻断神经胶质活性不会导致神经元或血流动力学活性发生变化。这些发作期的神经胶质波被间隙连接阻断剂甘诺索酮阻断。我们的体内数据表明，发作事件会触发缓慢传播的、典型的神经胶质钙波，由间隙连接介导，在空间和时间上独立于神经元和血流动力学活动。我们引入了一种新颖的发作触发传播神经胶质钙波，使人们对神经胶质钙波在发作发作和神经血管耦合中的重要性提出质疑。
It has been postulated that glia play a critical role in modifying neuronal activity, mediating neurovascular coupling, and in seizure initiation. We investigated the role of glia in ictogenesis and neurovascular coupling through wide-field multicell and 2-photon single cell imaging of calcium and intrinsic signal imaging of cerebral blood volume in an in vivo rat model of focal neocortical seizures. Ictal events triggered a slowly propagating glial calcium wave that was markedly delayed after both neuronal and hemodynamic onset. Glial calcium waves exhibited a stereotypical spread that terminated prior to seizure offset and propagated to an area similar to 60% greater than the propagation area of neural and vascular signals. Complete blockage of glial activity with fluoroacetate resulted in no change in either neuronal or hemodynamic activity. These ictal glial waves were blocked by carbenoxolone, a gap junction blocker. Our in vivo data reveal that ictal events trigger a slowly propagating, stereotypical glial calcium wave, mediated by gap junctions, that is spatially and temporally independent of neuronal and hemodynamic activities. We introduce a novel ictally triggered propagating glial calcium wave calling into question the criticality of glial calcium wave in both ictal onset and neurovascular coupling.