Westbrook G L, Lothman E W
Brain Res. 1983 Aug 22;273(1):97-109. doi: 10.1016/0006-8993(83)91098-3.
The effects of kainic acid (KA) were studied using extracellular and intracellular recordings in the hippocampal slice preparation. In sufficient concentrations, KA led to a loss of all evoked responses. However, the amount of drug needed for this varied according to anatomic region. CA3 was more sensitive (1 microM) than CA1 or the dentate gyrus (10 microM). These results can be understood in terms of a profound and long-lasting depolarization of neurons. Lower concentrations of KA (0.05-0.1 microM) did not change the resting membrane potential or input resistance of hippocampal pyramidal cells but produced spontaneous epileptiform activity which originated in CA3 and propagated to CA1. Epileptiform discharges were not present in the dentate gyrus. Coincident with the induction of paroxysms, the following changes were observed: (1) an increase in the excitability of CA3 and CA1 pyramidal cells as measured by a left shift in the input-output curves of evoked responses and a lowered threshold stimulus intensity necessary for activation of action potentials in single neurons; (2) augmentation and synchronization of bursting in pyramidal cells; and (3) prolonged EPSPs without an increase in their amplitude. These findings indicate that multiple changes, involving both the properties of single neurons and synaptic connections, are involved in the development of hippocampal paroxysms and that CA3 and CA1 have different roles in the generation of these discharges.
利用海马脑片制备技术中的细胞外和细胞内记录方法，研究了海藻酸（KA）的作用。在足够的浓度下，KA导致所有诱发反应消失。然而，产生这种作用所需的药物量因解剖区域而异。CA3比CA1或齿状回更敏感（1微摩尔），后者需要10微摩尔。这些结果可以从神经元的深度和持久去极化方面来理解。较低浓度的KA（0.05 - 0.1微摩尔）不会改变海马锥体细胞的静息膜电位或输入电阻，但会产生起源于CA3并传播至CA1的自发性癫痫样活动。齿状回中不存在癫痫样放电。与阵发性发作的诱导同时，观察到以下变化：（1）通过诱发反应的输入 - 输出曲线左移以及单个神经元中激活动作电位所需的阈值刺激强度降低来衡量，CA3和CA1锥体细胞的兴奋性增加；（2）锥体细胞爆发性放电的增强和同步化；（3）兴奋性突触后电位（EPSP）延长但幅度未增加。这些发现表明，海马阵发性发作的发展涉及多种变化，包括单个神经元的特性和突触连接，并且CA3和CA1在这些放电的产生中具有不同的作用。
