Normotopic Cortex Is the Major Contributor to Epilepsy in Experimental Double Cortex
Normotopic Cortex Is the Major Contributor to Epilepsy in Experimental Double Cortex
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DOI：
10.1002/ana.24237
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发表时间：
2014-09-01
影响因子：
11.2
通讯作者：
Manent, Jean-Bernard
中科院分区：
文献类型：
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作者：
Petit, Ludovic Franck;Jalabert, Marion;Manent, Jean-Bernard
目的：皮质下带状异位症是指新皮质神经元过早停止在白质中的迁移，在正常皮质下形成一条异位带而形成的皮质畸形，常与难治性癫痫有关。虽然很明显，波段异位和覆盖的皮质都有助于产生一种容易产生癫痫放电的异常电路，但人们对该电路的哪一部分最关键还知之甚少。在这里，我们试图在一种靶向的大鼠SBH遗传模型中确定癫痫样活动的起源。方法：通过将DCX基因导入大鼠胚胎新皮质祖细胞，通过敲除DCX基因而产生SBH大鼠(DCX-KD大鼠)。通过60通道微电极阵列的细胞外记录，分析荷包牡丹碱在新皮质脑片上诱导发作间歇样活动的来源、空间范围和层流轮廓。结果：条带异位不构成癫痫样电活动的主要来源，在体内诱发癫痫发作是必要的。此外，我们还报道了大多数起源于上皮层的发作间样放电继而传播到带状异位。重要的是，我们发现，在体内抑制SBH的神经元兴奋性并不改变DCX-KD大鼠表现癫痫的更高倾向。解释：这些结果表明，在SBH患者的大脑中，正常皮质比带状异位在产生发作间期癫痫样活动和癫痫发作中起主要作用。
Objective: Subcortical band heterotopia (SBH) is a cortical malformation formed when neocortical neurons prematurely stop their migration in the white matter, forming a heterotopic band below the normotopic cortex, and is generally associated with intractable epilepsy. Although it is clear that the band heterotopia and the overlying cortex both contribute to creating an abnormal circuit prone to generate epileptic discharges, it is less understood which part of this circuitry is the most critical. Here, we sought to identify the origin of epileptiform activity in a targeted genetic model of SBH in rats.Methods: Rats with SBH (Dcx-KD rats) were generated by knocking down the Dcx gene using shRNA vectors transfected into neocortical progenitors of rat embryos. Origin, spatial extent, and laminar profile of bicuculline-induced interictal-like activity on neocortical slices were analyzed by using extracellular recordings from 60-channel microelectrode arrays. Susceptibility to pentylenetetrazole-induced seizures was assessed by electrocorticography in head-restrained nonanesthetized rats.Results: We show that the band heterotopia does not constitute a primary origin for interictal-like epileptiform activity in vitro and is dispensable for generating induced seizures in vivo. Furthermore, we report that most interictal-like discharges originating in the overlying cortex secondarily propagate to the band heterotopia. Importantly, we found that in vivo suppression of neuronal excitability in SBH does not alter the higher propensity of Dcx-KD rats to display seizures.Interpretation: These results suggest a major role of the normotopic cortex over the band heterotopia in generating interictal epileptiform activity and seizures in brains with SBH.