GABAA receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex
GABAA receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex
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DOI：
10.1093/brain/awh181
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发表时间：
2004-07-01
期刊：
影响因子：
14.5
通讯作者：
Avoli, M
中科院分区：
文献类型：
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作者：
D'Antuono, M;Louvel, J;Avoli, M
泰勒型局灶性皮质发育不良 (FCD) 患者会出现癫痫发作，而这种癫痫发作往往是医学上难以治愈的。在这里，我们试图通过使用从患有 FCD 的癫痫患者获得的新皮质切片中的场电位和 K+ 选择性记录来确定导致这种癫痫状态的细胞和药理学机制，并且出于比较的目的，与内侧颞叶癫痫 (MTLE) 相比，MTLE 是一种癫痫疾病，至少在新皮质中，不以任何明显的神经元结构畸变为特征。 网络。通过应用含有 4-氨基吡啶 (4AP) 的培养基在体外诱导自发性癫痫样活动。在这些条件下，我们可以在 FCD 切片中识别出发作活动发作与缓慢发作间期样事件发生之间的密切时间关系，这主要是由 GABA(A) 受体激活引起的。我们还发现，在 FCD 切片中，能够减少或增加 GABA(A) 受体功能的药理学程序分别消除或增强了发作放电。此外，FCD 组织中发作事件的开始与 GABA(A) 受体依赖性发作间期事件的发生同时发生，导致 [K+](o) 升高高于发作间期期间所见的升高。最后，通过测试巴氯芬对 FCD 和 MTLE 切片产生的癫痫样事件的影响，我们发现 FCD 组织中 GABA(B) 受体（可能位于突触前抑制末端）的功能显着降低。因此，导致人 FCD 组织体外发作活动的癫痫样同步是由一种同步机制启动的，该机制矛盾地依赖于 GABA(A) 受体激活，导致 [K+](o) 大幅增加。 GABA(B) 受体控制中间神经元末端 GABA 释放的能力下降可能促进了这种机制。
Patients with Taylor's type focal cortical dysplasia (FCD) present with seizures that are often medically intractable. Here, we attempted to identify the cellular and pharmacological mechanisms responsible for this epileptogenic state by using field potential and K+-selective recordings in neocortical slices obtained from epileptic patients with FCD and, for purposes of comparison, with mesial temporal lobe epilepsy (MTLE), an epileptic disorder that, at least in the neocortex, is not characterized by any obvious structural aberration of neuronal networks. Spontaneous epileptiform activity was induced in vitro by applying 4-aminopyridine (4AP)-containing medium. Under these conditions, we could identify in FCD slices a close temporal relationship between ictal activity onset and the occurrence of slow interictal-like events that were mainly contributed by GABA(A) receptor activation. We also found that in FCD slices, pharmacological procedures capable of decreasing or increasing GABA(A) receptor function abolished or potentiated ictal discharges, respectively. In addition, the initiation of ictal events in FCD tissue coincided with the occurrence of GABA(A) receptor-dependent interictal events leading to [K+](o) elevations that were larger than those seen during the interictal period. Finally, by testing the effects induced by baclofen on epileptiform events generated by FCD and MTLE slices, we discovered that the function of GABA(B) receptors (presumably located at presynaptic inhibitory terminals) was markedly decreased in FCD tissue. Thus, epileptiform synchronization leading to in vitro ictal activity in the human FCD tissue is initiated by a synchronizing mechanism that paradoxically relies on GABA(A) receptor activation causing sizeable increases in [K+](o). This mechanism may be facilitated by the decreased ability of GABA(B) receptors to control GABA release from interneuron terminals.