NEURONAL EXCITABILITY IN CHRONIC EPILEPTOGENESIS

描述(申请人提供)：电生理和解剖学 将在创伤后癫痫大鼠模型上进行研究，以解决 脑内兴奋性和抑制性机制的变化问题 损伤后可能导致癫痫的新皮质。致痫灶 在成年大鼠中通过部分皮质分离产生 2-3周内出现异常放电。计划进行研究以评估改变 在GABA-A受体介导的抑制中，可能是由于 突触后神经元的氯化梯度，由于下调 钾/氯联合转运蛋白，KCC2。其他实验将评估兴奋性和 致痫灶内抑制性中间神经元的抑制性突触传入 大脑皮层，以检验这些细胞接受较少兴奋性和/或 更多的抑制性功能神经支配。在其他实验中，连接性 将对V层内的异常皮质进行研究，以确定 轴突萌发导致功能兴奋性连接异常。 采用的技术将包括免疫细胞化学，全细胞记录 皮层神经元的电流和电位，最小刺激和 扫描激光光解笼状谷氨酸的应用。结果是 与脑创伤后癫痫的发病机制有关。这个 长期目标是利用这些信息找到防止 创伤后癫痫。

DESCRIPTION (provided by applicant): Electrophysiological and anatomical studies will be done on a rat model of post-traumatic epilepsy to address questions of alterations in excitatory and inhibitory mechanisms within the neocortex that might lead to epilepsy following injury. Epileptogenic lesions are produced in adult rats by making partial cortical isolations that generate abnormal discharges within 2-3 weeks. Studies are planned to assess alterations in GABA-A receptor-mediated inhibition that might be produced by changes in the chloride gradient of post-synaptic neurons, due to a down regulation of the K/Cl co-transporter, KCC2. Other experiments will assess the excitatory and inhibitory synaptic inputs to inhibitory interneurons within the epileptogenic cortex, to test the hypothesis that these cells receive less excitatory and/or more inhibitory functional innervation. In other experiments, connectivity within layer V of the abnormal cortex will be studied to determine whether axonal sprouting results in abnormal functional excitatory connectivity. Techniques employed will include immunocytochemistry, whole cell recordings of currents and potentials in cortical neurons, minimal stimulation and the application of scanning laser photolysis of caged glutamate. Results are relevant to the mechanisms of epilepsy that develop following brain trauma. The long-term goal is to use this information to find strategies that will prevent post-traumatic epilepsy.