Acute Focal Seizures Start As Local Synchronizations of Neuronal Ensembles
Acute Focal Seizures Start As Local Synchronizations of Neuronal Ensembles
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DOI：
10.1523/jneurosci.3176-18.2019
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发表时间：
2019-10-23
影响因子：
5.3
通讯作者：
Yuste, Rafael
中科院分区：
文献类型：
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作者：
Wenzel, Michael;Hamm, Jordan P.;Yuste, Rafael
了解癫痫发作的形成和传播仍然是癫痫研究的关键目标。我们在雄性小鼠新皮质中使用快速体内双光子钙成像，以单细胞分辨率重建急性（4-氨基吡啶）局灶性皮质癫痫发作的动力学，因为它们起源于空间受限的癫痫发作起始部位（病灶内区域），随后传播到邻近的皮质区域（病灶外区域）。我们发现癫痫发作起源于起始部位内的局部神经元集合。这种异常的活动过度以跳跃的方式参与越来越大的区域，直到它闯入相邻的皮层，在那里它顺利进行，然后被电生理学检测到（LFP）。有趣的是，PV抑制性中间神经元在病灶内和病灶外区域具有空间异质性活动，排除了癫痫发作形成和扩散中抑制的简单作用。我们提出了一个两步模型局灶性癫痫发作的进展，其中神经元合奏激活第一，产生一个microseizure，其次是广泛的神经激活，通过相邻的皮层在macroseizures行波。
Understanding seizure formation and spread remains a critical goal of epilepsy research. We used fast in vivo two-photon calcium imaging in male mouse neocortex to reconstruct, with single-cell resolution, the dynamics of acute (4-aminopyridine) focal cortical seizures as they originate within a spatially confined seizure initiation site (intrafocal region), and subsequently propagate into neighboring cortical areas (extrafocal region). We find that seizures originate as local neuronal ensembles within the initiation site. This abnormal hyperactivity engages increasingly larger areas in a saltatory fashion until it breaks into neighboring cortex, where it proceeds smoothly and is then detected electrophysiologically (LFP). Interestingly, PV inhibitory interneurons have spatially heterogeneous activity in intrafocal and extrafocal territories, ruling out a simple role of inhibition in seizure formation and spread. We propose a two-step model for the progression of focal seizures, where neuronal ensembles activate first, generating a microseizure, followed by widespread neural activation in a traveling wave through neighboring cortex during macroseizures.