Enhanced interlaminar excitation or reduced superficial layer inhibition in neocortex generates different spike-and-wave-like electrographic events in vitro.
Enhanced interlaminar excitation or reduced superficial layer inhibition in neocortex generates different spike-and-wave-like electrographic events in vitro.
复制标题
新皮质层间兴奋增强或浅层抑制减少会在体外产生不同的尖波状电描记事件。
DOI：
10.1152/jn.00516.2017
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发表时间：
2018
影响因子：
2.5
通讯作者：
Whittington,MilesA
中科院分区：
文献类型：
--
作者：
Hall,StephenP;Traub,RogerD;Adams,NatalieE;Cunningham,MarkO;Schofield,Ian;Jenkins,AlistairJ;Whittington,MilesA
急性体外模型已经揭示了大量的信息，潜在的许多类型的癫痫样活动的机制。然而，很少有例子存在，揭示了尖峰和波（SpW）模式的病理活动。SpW见于许多癫痫综合征，包括全身性和局灶性，并在整个年龄范围内表现出来。它们在严重程度、症状负担和明显的解剖学来源（丘脑、新皮质或两者）方面是异质性的，但这种异质性与潜在病理学之间的任何关系仍然难以捉摸。在这项研究中，我们表明，生理δ频率节律作为一个有效的基板，允许建模的SpW的皮质起源，并可能有助于解决这个问题。对于δ活性的起始点，可以通过增强从新皮层层5上升到层2/3的兴奋性突触事件的幅度或选择性地修改表层GABA能抑制，在计算上和实验上对SpW的多个亚型进行建模。前者产生的SpW包含多个场尖峰，具有长的尖峰间隔，而后者产生的SpW具有短间隔的多个场尖峰。这两种类型有不同的层起源，每一个中断层间皮质动力学以不同的方式。少数来自不同诊断的患者的人类记录的例子显示SpW亚型具有相同的时间特征，这表明SpW放电中尖峰模式的详细量化可能是不同的潜在癫痫病理学的有用指标。新&值得注意的是尖峰和波型放电（SpW）是许多癫痫的共同特征。它们的电图表现是高度变化的，因为相关的潜在病理学的可用遗传线索。使用计算和体外模型，我们证明了不同亚型的SpW产生层选择性去抑制或增强层间激发。这些亚型可以在至少一些非侵入性患者记录中检测到，这表明更详细的SpW分析可能有助于确定临床病理学。
Acute in vitro models have revealed a great deal of information about mechanisms underlying many types of epileptiform activity. However, few examples exist that shed light on spike-and-wave (SpW) patterns of pathological activity. SpW are seen in many epilepsy syndromes, both generalized and focal, and manifest across the entire age spectrum. They are heterogeneous in terms of their severity, symptom burden, and apparent anatomical origin (thalamic, neocortical, or both), but any relationship between this heterogeneity and underlying pathology remains elusive. In this study we demonstrate that physiological delta-frequency rhythms act as an effective substrate to permit modeling of SpW of cortical origin and may help to address this issue. For a starting point of delta activity, multiple subtypes of SpW could be modeled computationally and experimentally by either enhancing the magnitude of excitatory synaptic events ascending from neocortical layer 5 to layers 2/3 or selectively modifying superficial layer GABAergic inhibition. The former generated SpW containing multiple field spikes with long interspike intervals, whereas the latter generated SpW with short-interval multiple field spikes. Both types had different laminar origins and each disrupted interlaminar cortical dynamics in a different manner. A small number of examples of human recordings from patients with different diagnoses revealed SpW subtypes with the same temporal signatures, suggesting that detailed quantification of the pattern of spikes in SpW discharges may be a useful indicator of disparate underlying epileptogenic pathologies.NEW & NOTEWORTHYSpike-and-wave-type discharges (SpW) are a common feature in many epilepsies. Their electrographic manifestation is highly varied, as are available genetic clues to associated underlying pathology. Using computational and in vitro models, we demonstrate that distinct subtypes of SpW are generated by lamina-selective disinhibition or enhanced interlaminar excitation. These subtypes could be detected in at least some noninvasive patient recordings, suggesting more detailed analysis of SpW may be useful in determining clinical pathology.