Dudek F E, Wuarin J P, Tasker J G, Kim Y I, Peacock W J
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523, USA.
J Neurosci Methods. 1995 Jun;59(1):49-58. doi: 10.1016/0165-0270(94)00193-k.
The recent emergence of surgical treatment of childhood epilepsy has led to the accessibility of young human cerebral tissue for electrophysiological studies of the mechanisms involved in epileptogenesis. Intracellular recordings were obtained from neurons in slices prepared from neocortical tissue resected from children (3 months to 15 years) with catastrophic epilepsy. Data from 'least abnormal' versus 'most abnormal' tissue were compared; the evaluation of the degree of abnormality was based on several clinical criteria. Hypotheses concerning NMDA receptors, local synaptic circuits, and epileptiform bursts were tested. The NMDA receptor-mediated component of synaptic responses, which was isolated pharmacologically, had a voltage dependence that was functionally mature by 8-10 months of age and did not appear to be altered even in the most abnormal tissue. Local inhibitory and excitatory synaptic circuits were present as early as 11 months and 8 months, respectively. Local excitatory circuits were sufficiently extensive in young children to initiate and sustain epileptiform activity when synaptic inhibition was suppressed. Bicuculline-induced epileptiform bursts were similar to those in adult human or animal neocortical slices. Burst duration and the presence of after-discharges were unrelated to patient age or tissue abnormality. These data demonstrate that (1) the electrophysiological properties of human neocortical neurons are very similar to those observed in animal experiments, (2) the mechanisms of neuronal communication are qualitatively mature within the first year of life, and (3) synaptic transmission and local neuronal circuits appear qualitatively normal, even in the most abnormal tissue from children with catastrophic epilepsy.
儿童癫痫外科治疗的近期出现，使得获取幼儿脑组织用于癫痫发生机制的电生理研究成为可能。从患有灾难性癫痫的儿童（3个月至15岁）切除的新皮质组织制备的切片中的神经元进行了细胞内记录。比较了“最正常”与“最异常”组织的数据；异常程度的评估基于多项临床标准。对有关NMDA受体、局部突触回路和癫痫样爆发的假设进行了测试。通过药理学分离的突触反应中NMDA受体介导的成分，其电压依赖性在8至10个月大时功能成熟，即使在最异常的组织中似乎也未改变。局部抑制性和兴奋性突触回路分别早在11个月和8个月时就已存在。当突触抑制被抑制时，幼儿的局部兴奋性回路足够广泛，能够引发和维持癫痫样活动。荷包牡丹碱诱导的癫痫样爆发与成人或动物新皮质切片中的相似。爆发持续时间和后放电的存在与患者年龄或组织异常无关。这些数据表明：（1）人类新皮质神经元的电生理特性与动物实验中观察到的非常相似；（2）神经元通讯机制在生命的第一年内定性成熟；（3）即使在患有灾难性癫痫的儿童最异常的组织中，突触传递和局部神经元回路在性质上似乎也是正常的。
