REGULATION OF NEURONAL EXCITABILITY IN CHRONIC EPILEPTOGENESIS

临床观察表明，皮质畸形是一种 癫痫发生发展中的重要病因 关于大脑皮质畸形的机制知之甚少 变得容易癫痫发作。计划中的实验 在大鼠大脑皮层建立局灶性微回模型 出生当天的经颅冷冻损伤。潜在的 病理学，当在成熟动物身上检查时，密切代表 人类的小脑回。电生理记录显示 紧邻小脑回的区域会产生 癫痫样物质被激活。计划中的实验将测试潜力 这种过度兴奋可能发生的机制，即 GABAA受体介导的抑制减少和增强 皮层内回路改变引起的兴奋性突触相互作用。 技术将涉及使用维持在脑部的新皮质切片 体外记录及膜片钳方法的应用 神经元自发和诱发的全细胞电流 可视化为“薄”切片和标准切片制剂。 神经解剖学研究将在充满生物细胞素的神经元上进行， 在实验中，正射和逆行示踪器将 用来检查小脑回内部和周围的连接性。这个 结果有望提供有关以下机制的新信息： 典型大脑皮层癫痫发病的研究进展 畸形。

Clinical observations suggest that cortical malformations are an important etiological factor in the development of epilepsy, yet little is known about the mechanisms by which malformed cortex becomes prone to epileptogenesis. The planned experiments employ a model of a focal microgyrus in rat neocortex produced by a transcranial freeze lesion on the day of birth. The underlying pathology, when examined in mature animals, closely represents that of human microgyri. Electrophysiological recordings show that the area immediately adjacent to the microgyrus generates epileptiform activates. The planned experiments will test potential mechanisms by which this hyperexcitability might occur, namely a decrease in GABAa receptor-mediated inhibition and enhanced excitatory synaptic interactions due to altered intracortical circuitry. Techniques will involve use of neocortical slices maintained in vitro, and application of patch-clamp methods for recording spontaneous and evoked whole cell currents from neurons visualized in 'thin' slices, and those in standard slice preparations. Neuroanatomic studies will be done on neurons filled with biocytin, and in experiments where orthograde and retrograde tracers will be used to examine connectivity in and around the microgyrus. The results promise to provide new information about mechanisms for development of epileptogenesis in a prototypic cortical malformation.