Li Y, Evans M S, Faingold C L
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794.
Brain Res. 1994 Oct 17;660(2):232-40. doi: 10.1016/0006-8993(94)91294-7.
Previous studies using single-unit recording techniques have shown that the inferior colliculus is critical for audiogenic seizure initiation in genetically epilepsy-prone rats (GEPR). In order to investigate cellular abnormalities that may be important in causing audiogenic seizure susceptibility, intracellular recordings were made from neurons of inferior colliculus dorsal cortex (ICd) in a GEPR variety that exhibits severe audiogenic seizures (GEPR-9). GEPR neuronal membrane and synaptic properties were compared to those of normal Sprague-Dawley rats (SD), the strain from which GEPR were derived. We found six electrophysiological differences between GEPR and normal SD ICd neurons, all of which could promote seizures in GEPR. (1) Input resistance was higher in GEPR than in normal ICd neurons. (2) Threshold for repetitive action potential firing was closer to resting membrane potential in GEPR ICd neurons. (3) GEPR neurons showed faster repetitive spike firing than normal SD neurons. (4) Anode break spikes occurred at the offset of a hyperpolarizing pulse more often in GEPR than in normal SD neurons. (5) Stimulation of the commissure of the inferior colliculus caused synaptic paired pulse inhibition in normal ICd neurons, but paired pulse facilitation was always observed in GEPR neurons. (6) In GEPR, a large epileptiform depolarizing event could be elicited by strong electrical stimulation of the commissure of the inferior colliculus. In normal SD rats, similar epileptiform activity was seen only after application of bicuculline or NMDA. Our results suggest that both abnormal neuronal membrane properties and altered synaptic transmission are likely to contribute to seizure predisposition and audiogenic seizure initiation in GEPR.
以往使用单单位记录技术的研究表明，下丘对于遗传性癫痫易感大鼠（GEPR）的听源性癫痫发作起始至关重要。为了研究可能在导致听源性癫痫易感性方面起重要作用的细胞异常，我们对一种表现出严重听源性癫痫发作的GEPR品系（GEPR-9）的下丘背侧皮质（ICd）神经元进行了细胞内记录。将GEPR神经元的膜和突触特性与正常的斯普拉格-道利大鼠（SD）（GEPR的起源品系）的特性进行了比较。我们发现GEPR和正常SD的ICd神经元之间存在六个电生理差异，所有这些差异都可能促使GEPR发生癫痫发作。（1）GEPR的输入电阻高于正常ICd神经元。（2）GEPR的ICd神经元重复动作电位发放的阈值更接近静息膜电位。（3）GEPR神经元比正常SD神经元表现出更快的重复锋电位发放。（4）GEPR神经元比正常SD神经元更频繁地在下丘连合刺激引起的超极化脉冲结束时出现阳极断裂锋电位。（5）刺激下丘连合在正常ICd神经元中引起突触成对脉冲抑制，但在GEPR神经元中总是观察到成对脉冲易化。（6）在GEPR中，强烈电刺激下丘连合可引发大的癫痫样去极化事件。在正常SD大鼠中，仅在应用荷包牡丹碱或N-甲基-D-天冬氨酸后才观察到类似的癫痫样活动。我们的结果表明，异常的神经元膜特性和改变的突触传递都可能导致GEPR的癫痫易感性和听源性癫痫发作起始。
