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印防己毒素诱导的海马癫痫样活动:内源性因素与突触因素的作用

Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors.

作者信息

Hablitz J J

出版信息

J Neurophysiol. 1984 May;51(5):1011-27. doi: 10.1152/jn.1984.51.5.1011.

DOI:10.1152/jn.1984.51.5.1011
PMID:6327932
Abstract

Picrotoxin-(PTX) induced epileptiform activity was studied in guinea pig hippocampal slices maintained in vitro, using intra- and extracellular recording techniques. The observed pattern of spontaneous and evoked epileptiform activity was quite complex. Spontaneous epileptiform events originated in the CA3 region and subsequently spread or propagated to CA1. Activation of CA1 could then reactivate CA3. This reverberation of activity was seen also following stimulation of the mossy fiber afferents from the dentate gyrus to CA3. Stimulation of fibers in the stratum radiatum of the CA1 region could trigger, at short latency, epileptiform activity that either was localized in CA1 or also occurred in CA3, with a late secondary discharge in CA1. This is attributed to a backfiring of the Schaffer collaterals and illustrates the ability of a variety of CA3 inputs to trigger epileptiform activity. Bath-applied PTX, at concentrations of 50-200 microM, had no apparent effect on the resting membrane potential or input resistance of the CA3 cells tested. Depolarizing current pulses elicited characteristic endogenous-burst responses that were not altered by PTX. Synaptic activity evoked by mossy fiber stimulation was altered markedly by PTX. The pattern of observed changes indicated that PTX reduced inhibitory postsynaptic potential (IPSP) amplitudes, resulting in the appearance of repetitive (presumably recurrent) excitatory inputs. Paroxysmal depolarizing shifts ( PDSs ) were generated by the coalescence of these excitatory inputs. Two types of spontaneous bursting were observed after PTX application. The first type was nonepileptiform , all or none in nature, and its frequency was voltage dependent. The second type of spontaneous burst was the PDS. It was epileptiform in character because it was associated with the synchronous discharge of many neurons. It was graded in nature, and its frequency was voltage independent. The graded nature of the PDS was demonstrated by varying the duration and intensity of the orthodromic stimulation. Trains of stimulation could produce PDSs that lasted 500-800 ms. A refractory period was observed following a PDS. By varying the strength of the orthodromic stimulation, it was possible to demonstrate that for the intervals tested this was a relative, not absolute, refractory period. Intracellular recordings in CA3 neurons indicated that each spontaneous PDS was followed by an afterhyperpolarization (AHP).

摘要

利用细胞内和细胞外记录技术,对体外培养的豚鼠海马切片中印防己毒素(PTX)诱导的癫痫样活动进行了研究。观察到的自发和诱发癫痫样活动模式相当复杂。自发癫痫样事件起源于CA3区,随后扩散或传播至CA1区。CA1区的激活随后可重新激活CA3区。在刺激从齿状回至CA3区的苔藓纤维传入纤维后,也可观察到这种活动的反复回荡。刺激CA1区辐射层中的纤维可在短潜伏期触发癫痫样活动,该活动要么局限于CA1区,要么也出现在CA3区,并在CA1区出现延迟的继发性放电。这归因于Schaffer侧支的逆行放电,并说明了多种CA3输入触发癫痫样活动的能力。以50 - 200微摩尔浓度浴加PTX,对所测试的CA3细胞的静息膜电位或输入电阻无明显影响。去极化电流脉冲引发特征性的内源性爆发反应,且不受PTX影响。苔藓纤维刺激诱发的突触活动被PTX显著改变。观察到的变化模式表明,PTX降低了抑制性突触后电位(IPSP)的幅度,导致出现重复性(可能是反复性)兴奋性输入。这些兴奋性输入的合并产生了阵发性去极化偏移(PDS)。施加PTX后观察到两种类型的自发放电。第一种类型是非癫痫样的,本质上是全或无的,其频率与电压相关。第二种类型的自发放电是PDS。它具有癫痫样特征,因为它与许多神经元的同步放电有关。它本质上是分级的,其频率与电压无关。通过改变顺向刺激的持续时间和强度证明了PDS的分级性质。一连串刺激可产生持续500 - 800毫秒的PDS。在PDS后观察到一个不应期。通过改变顺向刺激的强度,可以证明在所测试的间隔内这是一个相对而非绝对的不应期。CA3神经元的细胞内记录表明,每个自发PDS之后都有一个超极化后电位(AHP)。

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