REGULATION OF NEURONAL EXCITABILITY IN CHRONIC EPILEPTOGENESIS

临床观察表明，皮质畸形是一种 癫痫的发病机制有哪些？ 我们对畸形皮层 变得容易癫痫发作。 计划中的实验 采用大鼠新皮层中的局灶性微回模型， 在出生当天就出现了经颅冷冻损伤底层 病理学，当在成熟动物中检查时， 人类大脑小回的结构。 电生理记录显示 与大脑微回紧邻的区域 癫痫发作 计划中的实验将测试 这种过度兴奋可能发生的机制，即 减少GABA α受体介导的抑制， 兴奋性突触的相互作用，由于改变皮质内电路。 技术将涉及使用新皮层切片， 应用膜片钳技术记录 来自神经元的自发和诱发全细胞电流 在“薄”切片中可视化，以及在标准切片制备中可视化。 神经解剖学研究将在充满生物胞素的神经元上进行， 在实验中，顺行和逆行示踪剂将 用来检查微脑回内部和周围的连通性。 的 研究结果有望提供有关 癫痫发生在一个原型皮质 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.