PICROTOXIN-INDUCED EPILEPTIFORM ACTIVITY IN HIPPOCAMPUS - ROLE OF ENDOGENOUS VERSUS SYNAPTIC FACTORS
PICROTOXIN-INDUCED EPILEPTIFORM ACTIVITY IN HIPPOCAMPUS - ROLE OF ENDOGENOUS VERSUS SYNAPTIC FACTORS
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DOI：
10.1152/jn.1984.51.5.1011
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发表时间：
1984-01-01
影响因子：
2.5
通讯作者：
HABLITZ, JJ
中科院分区：
文献类型：
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作者：
HABLITZ, JJ
采用细胞内和细胞外记录技术，研究了印防己毒素（PTX）对离体培养的豚鼠海马脑片的致痫作用。观察到的自发和诱发癫痫样活动的模式是相当复杂的。自发性癫痫样事件起源于CA 3区，随后扩散或传播到CA 1区。CA 1的激活可以重新激活CA 3。在刺激从齿状回到CA 3的苔藓纤维传入后，也观察到这种活动的回响。在CA 1区的辐射层中的纤维的刺激可以触发，在短潜伏期，癫痫样活动，无论是本地化在CA 1或也发生在CA 3，在CA 1的晚期二次放电。这归因于Schaffer侧支的逆火，并说明了各种Ca 3输入触发癫痫样活动的能力。在50-200 μ M浓度下，连续施用的PTX对测试的CA 3细胞的静息膜电位或输入电阻没有明显的影响。去极化电流脉冲引起特征性的内源性爆发反应，而这种反应不被紫杉醇改变。刺激苔藓纤维诱发的突触活动被PTX显著改变。观察到的变化的模式表明，PTX抑制性突触后电位（IPSP）的幅度降低，导致重复（可能是经常性的）兴奋性输入的外观。阵发性去极化位移（PDS）产生的合并这些兴奋性输入。应用PTX后观察到两种类型的自发爆发。第一种类型是非癫痫样的，全部或没有性质，其频率是电压依赖性的。第二类自发性爆破是PDS。这是癫痫样的特点，因为它与许多神经元的同步放电。它在性质上是分级的，其频率与电压无关。PDS的分级性质通过改变顺向刺激的持续时间和强度来证明。列车的刺激可以产生PDS持续500-800毫秒。观察到一个不应期后PDS。通过改变顺向刺激的强度，可以证明对于测试的间隔，这是相对而非绝对的不应期。在CA 3神经元的细胞内记录表明，每个自发PDS后超极化（AHP）。AHP衰减时间和PDS间隔的定量测量分析表明，这些变量之间没有显着的相关性。通过手术将海马切片分成2半。其中一半由CA 2 -3的分离片段组成，而另一半包含来自CA 1和齿状回的组织。暴露于戊四氮而非青霉素后，每个分离的节段均表现出自发性癫痫样放电。孤立以及完整的CA 3子字段显示了显着的周期性癫痫样放电率。与此相反，孤立的CA 1区有一个非周期性率显着较长的癫痫样事件之间的间隔。PDS的产生可能是由于反复兴奋性输入的积累。突触相互作用在癫痫发生中的重要作用是由一连串刺激的结果说明的。反复出现的兴奋性连接的模式和数量以及抑制和兴奋的相对平衡似乎是决定自发性癫痫样活动的发生和性质的重要因素。
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 .mu.M, 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 (PDS) were generated by the coalescence of these excitatory inputs. Two types of spontaneous bursting were observed after PTX application. The 1st type was nonepileptiform, all or none in nature, and its frequency was voltage dependent. The 2nd 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 PDS 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). Analysis of quantitative measurements of AHP decay time and inter-PDS interval indicated that there was no significant correlation between these variables. Hippocampal slices were divided surgically into 2 halves. One half consisted of isolated segments of CA2-3, whereas the other contained tissue from CA1 and dentate gyrus. After exposure to PTX but not penicillin, each isolated segment displayed spontaneous epileptiform discharges. Isolated as well as intact CA3 subfields displayed a marked periodicity in epileptiform discharge rate. In contrast, isolated CA1 regions had an aperiodic rate of significantly longer intervals between epileptiform events. Probably PDS generation results from the buildup of recurrent excitatory inputs. The important role of synaptic interactions in epileptogenesis is illustrated by the results with trains of stimuli. The pattern and number of recurrent excitatory connections, and the relative balance of inhibition and excitation appear to be the important factors in determining the occurrence and nature of spontaneous epileptiform activity.