Axon terminal hyperexcitability associated with epileptogenesis in vitro. I. Origin of ectopic spikes.
Axon terminal hyperexcitability associated with epileptogenesis in vitro. I. Origin of ectopic spikes.
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轴突末端过度兴奋与体外癫痫发生相关。
DOI：
10.1152/jn.1993.70.3.961
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发表时间：
1993
影响因子：
2.5
通讯作者：
Wilson,WA
中科院分区：
文献类型：
--
作者：
Stasheff,SF;Hines,M;Wilson,WA
1.细胞内和细胞外记录技术用于研究异位（即，在海马切片的这个亚群中，在电描记癫痫发作（EGS）的点燃样诱导期间，在CA 3锥体细胞之间发生动作电位产生。点燃样刺激序列（60 Hz，2 s）被递送至s。每隔10分钟，对CA 3区放射状突起进行一次扫描。随着EGS的发展，异位放电频率显著增加（10.33 ± 3.29峰/min，平均值± SE，P < 0.01）。应用几种方法来确定细胞内这些动作电位的起始位点（轴突与树突）。2.在CA 3细胞中已知的逆向和顺向动作电位之间进行碰撞测试，以确定碰撞的临界期c。然后尝试使异位尖峰与已知的逆向动作电位相碰撞。在小于c的间隔，异位棘波未能与逆行的碰撞，在10例中的5例。在这些细胞中，这清楚地表明，异位尖峰本身的轴突起源。在其余5例中，异位尖峰与逆向动作电位以约等于c的间隔发生碰撞，这很可能是因为CA 3中复发性轴突侧支的复杂系统内的相互作用。3.用神经元房室模型模拟CA 3区锥体细胞的动作电位。这些模拟是基于CA 3锥体神经元和运动神经元动作电位的先前模型。在轴突隔室中产生的模拟动作电位在其上升相（IS-SD中断）上具有显著的拐点，这在体细胞或树突隔室中产生的尖峰中难以理解。4.从CA 3锥体细胞实验记录的动作电位的分析也表明，逆向尖峰具有突出的IS-SD打破，是不存在于顺向尖峰。除了确定的逆向动作电位，异位棘波也具有这样的拐点。与计算机模拟的预测一起，该分析还表明，异位尖峰起源于CA 3细胞的轴突。5.通过压力注射局部应用河豚毒素（TTX，50 μ M），同时监测异位峰电位活性。局部应用TTX的切片区域，可以包括轴突，但不记录细胞的树突废除或显着降低异位尖峰的频率（n = 5），进一步证实了这一假设，这些动作电位产生的CA 3轴突。（400字处截断摘要）
1. Intracellular and extracellular recording techniques were used to study the increase in ectopic (i.e., nonsomatic) action-potential generation occurring among CA3 pyramidal cells during the kindling-like induction of electrographic seizures (EGSs) in this subpopulation of the hippocampal slice. Kindling-like stimulus trains (60 Hz, 2 s) were delivered to s. radiatum of CA3 at 10-min intervals. As EGSs developed, the frequency of ectopic firing increased markedly (by 10.33 +/- 3.29 spikes/min, mean +/- SE, P << 0.01). Several methods were applied to determine the initiation site for these action potentials within the cell (axons vs. dendrites). 2. Collision tests were conducted between known antidromic and orthodromic action potentials in CA3 cells to determine the critical period, c, for collision. Attempts were then made to collide ectopic spikes with known antidromic action potentials. At intervals less than c, ectopic spikes failed to collide with antidromic ones, in 5 of 10 cases. In these cells, this clearly indicates that the ectopic spikes were themselves of axonal origin. In the remaining five cases, ectopic spikes collided with antidromic action potentials at intervals approximately equal to c, most likely because of interactions within the complex system of recurrent axon collaterals in CA3. 3. Action potentials of CA3 pyramidal cells were simulated with the use of a compartmental computer model, NEURON. These simulations were based on prior models of CA3 pyramidal neurons and of the motoneuron action potential. Simulated action potentials generated in axonal compartments possessed a prominent inflection on their rising phase (IS-SD break), which was difficult to appreciate in those spikes generated in somatic or dendritic compartments. 4. An analysis of action potentials recorded experimentally from CA3 pyramidal cells also showed that antidromic spikes possess a prominent IS-SD break that is not present in orthodromic spikes. In addition to identified antidromic action potentials, ectopic spikes also possess such an inflection. Together with the predictions of computer simulations, this analysis also indicates that ectopic spikes originate in the axons of CA3 cells. 5. Tetrodotoxin (TTX, 50 microM) was locally applied by pressure injection while monitoring ectopic spike activity. Localized application of TTX to regions of the slice that could include the axons but not the dendrites of recorded cells abolished or markedly reduced the frequency of ectopic spikes (n = 5), further confirming the hypothesis that these action potentials arise from CA3 axons.(ABSTRACT TRUNCATED AT 400 WORDS)