Ictal epileptiform activity is facilitated by hippocampal GABAA receptor-mediated oscillations
Ictal epileptiform activity is facilitated by hippocampal GABAA receptor-mediated oscillations
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DOI：
10.1523/jneurosci.20-18-06820.2000
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发表时间：
2000-09-15
影响因子：
5.3
通讯作者：
Jefferys, JGR
中科院分区：
文献类型：
--
作者：
Köhling, R;Vreugdenhil, M;Jefferys, JGR
短暂间歇放电向长时间癫痫发作转变的细胞和网络机制是癫痫的一个关键问题。在这里，我们使用暴露于含有0 Mg2+的ACSF的海马切片来探索过渡到长时间（3-42秒）癫痫样（“发作”）放电的机制。在50-60%的成年和幼年大鼠（出生后13-21天）切片中，谢弗侧枝刺激诱发的癫痫样活动引发了CA1的长时间爆发。在这些病例中，CA1癫痫样爆发的第一个组成部分是在伽马波段及以上频率（30-120 Hz，让人想起破伤风诱发的伽马振荡）的一系列群体尖峰。伽马射线爆发之后可能会出现较慢的重复“第三纪”射线爆发。CA1在γ期的细胞内记录显示长时间的去极化，动作电位从短暂的明显超极化上升，输入电阻下降。双球茎碱（10-50 μ M）和乙氧基唑胺（100 mM）完全阻断CA1 γ节律，高渗灌注液（50 mM蔗糖）强烈减弱CA1 γ节律。随后的第三次爆发也被二胡兰、乙氧基唑胺和高渗性灌注液阻断。在所有这些病例中，CA3的细胞内记录仅显示短暂的去极化。我们得出结论，在癫痫发病条件下，伽马波段振荡是由GABA(A)能量去极化引起的，这种活动可能导致产生临界放电。
The cellular and network mechanisms of the transition of brief interictal discharges to prolonged seizures are a crucial issue in epilepsy. Here we used hippocampal slices exposed to ACSF containing 0 Mg2+ to explore mechanisms for the transition to prolonged (3-42 sec) seizure-like ("ictal") discharges. Epileptiform activity, evoked by Shaffer collateral stimulation, triggered prolonged bursts in CA1, in 50-60% of slices, from both adult and young (postnatal day 13-21) rats. In these cases the first component of the CA1 epileptiform burst was followed by a train of population spikes at frequencies in the gamma band and above (30-120 Hz, reminiscent of tetanically evoked gamma oscillations). The gamma burst in turn could be followed by slower repetitive "tertiary" bursts. Intracellular recordings from CA1 during the gamma phase revealed long depolarizations, action potentials rising from brief apparent hyperpolarizations, and a drop of input resistance. The CA1 gamma rhythm was completely blocked by bicuculline (10-50 mu M), by ethoxyzolamide (100 mM), and strongly attenuated in hyperosmolar perfusate (50 mM sucrose). Subsequent tertiary bursts were also blocked by bicuculline, ethoxyzolamide, and in hyperosmolar perfusate. In all these cases intracellular recordings from CA3 revealed only short depolarizations. We conclude that under epileptogenic conditions, gamma band oscillations arise from GABA(A) ergic depolarizations and that this activity may lead to the generation of ictal discharges.