Reliable and Elastic Propagation of Cortical Seizures In Vivo.
Reliable and Elastic Propagation of Cortical Seizures In Vivo.
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DOI：
10.1016/j.celrep.2017.05.090
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发表时间：
2017-06-27
期刊：
影响因子：
8.8
通讯作者：
Yuste R
中科院分区：
文献类型：
--
作者：
Wenzel M;Hamm JP;Peterka DS;Yuste R
绘制癫痫基础的精细神经活动是确定这种常见难治性疾病的潜在控制目标的关键。然而，在皮质微电路癫痫发作进展的详细体内动力学仍然知之甚少。我们结合联合收割机快速双光子钙成像（30-Hz）与LFP记录，逐细胞绘制局部诱导（4-AP或印防己毒素）癫痫发作在麻醉和清醒小鼠中的扩散。使用单层和微棱镜辅助多层成像在不同的皮层区域，我们发现可靠的招聘和跨皮质层内的本地神经种群，并找到层特定的时间延迟，表明最初的颗粒上的入侵，然后由深层招聘在横向癫痫蔓延。有趣的是，尽管进展途径一致，但连续癫痫发作显示出明显的时间变异性，这主要取决于GABA能抑制。我们提出了一个类似于弹性网络的癫痫电路模型，其中发作进展忠实地遵循预先存在的途径，但在时间上灵活变化，这取决于当地的抑制性约束。Wenzel等人在体内绘制了细胞分辨率下的皮质癫痫发作扩散图，并表明癫痫发作扩散可靠，具有重复的细胞和分层募集模式，但在绝对时间内募集持续时间差异很大。这种“弹性”是由抑制性中间神经元控制的，因为局部GABAA-R阻断消除了这种现象。
Mapping the fine-scale neural activity that underlies epilepsy is key to identify potential control targets of this frequently intractable disease. Yet, the detailed in vivo dynamics of seizure progression in cortical microcircuits remain poorly understood. We combine fast two-photon calcium imaging (30-Hz) with LFP recordings to map, cell by cell, the spread of locally induced (4-AP or picrotoxin) seizures in anesthetized and awake mice. Using single-layer and microprism-assisted multi-layer imaging in different cortical areas we uncover reliable recruitment of local neural populations within and across cortical layers, and find layer-specific temporal delays, suggesting an initial supra-granular invasion followed by deep-layer recruitment during lateral seizure spread. Intriguingly, despite consistent progression pathways, successive seizures show pronounced temporal variability that critically depends on GABAergic inhibition. We propose an epilepsy circuit model resembling an elastic meshwork wherein ictal progression faithfully follows preexistent pathways but varies flexibly in time, depending on the local inhibitory restraint. Wenzel et al. map cortical seizure spread at cellular resolution in vivo, and show that seizures spread reliably, with repeated cell-wise and layer-wise recruitment patterns, yet with greatly variable recruitment durations in absolute time. This ‘elasticity’ is controlled by inhibitory interneurons, as local GABAA-R blockade abolishes the phenomenon.
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