MECHANISMS OF NEOCORTICAL EPILEPTOGENESIS INVITRO
MECHANISMS OF NEOCORTICAL EPILEPTOGENESIS INVITRO
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DOI：
10.1152/jn.1982.48.6.1321
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发表时间：
1982-01-01
影响因子：
2.5
通讯作者：
PRINCE, DA
中科院分区：
文献类型：
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作者：
GUTNICK, MJ;CONNORS, BW;PRINCE, DA
在豚鼠新皮质的体外脑片标本中研究了发作间期癫痫发生的细胞机制。将青霉素或荷包牡丹碱应用于组织，并从神经元和神经胶质细胞获取细胞内记录。在应用惊厥剂后，刺激可在单个神经元中引发短潜伏期兴奋性突触后电位（EPSP）和一个大的、较长潜伏期的去极化漂移（DS）。脑片中神经元的DS与体内新皮质神经元中诱发的DS非常相似，因为它们表现出全或无的特性、在重复刺激期间潜伏期的大幅变化、长时程后电位和延长的不应期。与完整皮质中青霉素诱发的癫痫发生相反，在新皮质脑片中既未观察到自发性DS，也未观察到发作期。在同一皮质柱内成对神经元的同时记录中，DS的产生和潜伏期变化总是同步的。神经元中DS的产生也与细胞外[K⁺]的阵发性大幅增加同时发生，这从神经胶质细胞的同时记录中可以看出。当向注射了局部麻醉剂QX - 314[（2 -（三乙胺）- N - 2,6 - 二甲基苯乙酰胺）]的神经元施加极化电流时，DS幅度单调变化，外推的反转电位接近0 mV。在注射了K⁺电流阻断剂Cs⁺的神经元中，膜电位可能有较大位移，并且在约0 mV时，短潜伏期EPSP和DS的峰值完全消失。在此电位之上，短潜伏期EPSP反转，DS被阵发性超极化所取代，其上升时间和峰值潜伏期与静息电位下诱发的DS相比延长。阵发性超极化可能代表了EPSP对被穿刺神经元的长时间激活。电压依赖性成分，包括慢波峰，似乎在填充Cs⁺的细胞静息电位下对DS的产生有贡献，并且这些成分在大的去极化过程中被阻断。单个新皮质神经元中DS的产生可能发生在一大组细胞的同步突触激活期间。给定神经元中DS的起始由与短潜伏期EPSP不同的可变潜伏期兴奋性输入的时间决定。DS的缓慢包络似乎是由长时间的兴奋性突触电流产生的，并可能受到内在的电压依赖性膜电导的调节。基于新皮质内在回路的解剖学和生理学组织，提出了一个关于DS起始的假说。
The cellular mechanisms underlying interictal epileptogenesis was examined in an in vitro slice preparation of guinea pig neocortex. Penicillin or bicuculline was applied to the tissue, and intracellular recordings were obtained from neurons and glia. Following convulsant application, stimulation could elicit a short-latency excitatory postsynaptic potential (EPSP) and a large, longer latency depolarization shift (DS) in single neurons. DS in neurons of the slice were very similar to those evoked in neurons of neocortex in vivo in that they displayed an all-or-none character, large shifts in latency during repetitive stimuli, long afterpotentials and a prolonged refractory period. In contrast to epileptogenesis produced by penicillin in intact cortex, neither spontaneous DS nor ictal episodes were observed in neocortical slices. In simultaneous recordings from pairs of neurons within the same cortical column, DS generation and latency shifts were invariably synchronous. DS generation in neurons was also coincident with large, paroxysmal increases of extracellular [K+], as indicated by simultaneous recordings from glia. When polarizing currents were applied to neurons injected with the local anesthetic QX-314 [(2-(triethylamine)-N-2,6-dimethylphenylacetamide)], the DS amplitude varied monotonically and had an extrapolated reversal potential near 0 mV. In neurons injected with the K+-current blocker Cs+, large displacements of membrane potential were possible and both the short-latency EPSP and the peak of the DS diminished completely at .apprx. 0 mV. At potentials positive to this, the short-latency EPSP was reversed and the DS was replaced by a paroxysmal hyperpolarization whose rise time and peak latency were prolonged compared to the DS evoked at resting potential. The paroxysmal hyperpolarization probably represents the prolonged activation of the impaled neuron by EPSP. Voltage-dependent components, including slow spikes, appeared to contribute to generation of the DS at resting potential in Cs+-filled cells, and these components were blocked during large depolarizations. DS generation in single neocortical neurons probably occurs during synchronous synaptic activation of a large group of cells. DS onset in a given neuron is determined by the timing of a variable-latency excitatory input that differs from the short-latency EPSP. The DS slow envelope appears to be generated by long-duration excitatory synaptic currents and may be modulated by intrinsic voltage-dependent membrane conductances. A hypothesis for the initiation of the DS, based on the anatomical and physiological organization of the intrinsic neocortical circuits, is presented.