Fast Activity at Seizure Onset Is Mediated by Inhibitory Circuits in the Entorhinal Cortex In Vitro

Fast Activity at Seizure Onset Is Mediated by Inhibitory Circuits in the Entorhinal Cortex In Vitro
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DOI:
10.1002/ana.21519
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发表时间:
2008-12-01
影响因子:
11.2
通讯作者:
de Curris, Marco
de Curris, Marco
中科院分区:
医学1区
文献类型:
--
作者:
Gnatkovsky, Vadym;Librizzi, Laura;de Curris, Marco

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目的:局灶性癫痫发作启动的网络机制仍不清楚。在内侧颞叶癫痫患者中进行的诊断性颅内记录期间观察到的一种常见癫痫发作模式的特征在于20至30 Hz的快速活动。我们再现了20至30 Hz的振荡在癫痫发作发作时在颞叶的离体豚鼠脑研究参与其generation.Methods的细胞和网络机制:癫痫样活动诱导在离体脑由3分钟的动脉灌注50 μ M荷包牡丹碱。同时进行细胞内,细胞外,和离子选择性电生理记录在内嗅皮层(EC)在interictal-ictal transition.Results:EC的深,浅层的主要神经元不产生动作电位在拳头活动在发作onset. Results,而持续放电观察假定的中间神经元。在癫痫发作开始后的5到10秒内,主神经元产生了一个突出的放电,与细胞外超同步爆发放电的出现相关。在浅表神经元,拳头活动与节奏IPSPs,在一个缓慢的去极化与增加胞外kotalin.Interpretation:我们得出结论,在一个急性模型的颞叶ictogenesis,持续的抑制,而不发射EC主神经元与局灶性癫痫发作的发病过程中的振幅逐渐下降。发作性放电的进展是由抑制性突触后电位的逆转电位的钾依赖性变化贡献的。这些研究结果表明,在过渡到癫痫发作的EC抑制网络的突出作用。
Objective: Network mechanisms responsible for focal seizure initiation are still largely unknown. One of the prevalent seizure patterns observed during diagnostic intracranial recordings performed in patients with mesial temporal lobe epilepsy is characterized by fast activity at 20 to 30Hz. We reproduced 20 to 30Hz oscillations at seizure onset in the temporal lobe of the in vitro isolated guinea pig brain to study cellular and network mechanisms involved in its generation.Methods: Seizure-like activity was induced in the isolated brain by 3-minute arterial perfusion of 50 mu M bicuculline. Intracellular, extracellular, and ion-selective electrophysiological recordings were performed simultaneously in the entorhinal cortex (EC) during interictal-ictal transition.Results: Principal neurons in deep and superficial layers of the EC did not generate action potentials during fist activity at ictal onset, whereas sustained firing was observed in putative interneurons. Within 5 to 10 seconds from seizure initiation, principal neurons generated a prominent firing that correlated with the appearance of extracellular hypersynchronous bursting discharges. In superficial neurons, fist activity correlated with rhythmic IPSPs that progressively decreased in amplitude during the development of a slow depolarization associated with an increase in extracellular potassium.Interpretation: We conclude that in an acute model of temporal lobe ictogenesis, sustained inhibition without firing of EC principal neurons correlates with the onset of a focal seizure. The progression of the ictal discharge is contributed by a potassium-dependent change in reversal potential of inhibitory postsynaptic potentials. These findings demonstrate a prominent role of inhibitory networks during the transition to seizure in the EC.