NEURONAL EXCITABILITY IN CHRONIC EPILEPTOGENESIS

慢性癫痫发生中的神经元兴奋性

• 批准号: 6989025
• 负责人: David Allan Prince
• 金额: $ 47.2万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989025
• 关键词: GABA receptor; brain electrical activity; cell population study; disease /disorder model; epilepsy; evoked potentials; experimental brain lesion; gene expression; immunocytochemistry; laboratory rat; microscopy; molecular pathology; neocortex; neural conduction; neural inhibition; neural transmission; neuroanatomy; neurogenetics; neurons; neuroregulation; protein structure function; receptor coupling; sodium potassium exchanging ATPase; synapses; voltage /patch clamp

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.

描述（由申请人提供）：电生理学和解剖学 将在创伤后癫痫大鼠模型上进行研究， 问题的兴奋和抑制机制的改变， 可能导致损伤后癫痫的新皮层。致痫性病变 在成年大鼠中产生， 2-3周内出现异常分泌物。计划进行研究，以评估 在GABA-A受体介导的抑制中， 氯梯度突触后神经元，由于下调 K/Cl协同转运蛋白，KCC 2。其他实验将评估兴奋性和 抑制性突触输入到致痫神经元内的抑制性中间神经元 皮质，以检验这些细胞接受较少兴奋性和/或 更多的抑制性功能性神经支配。在其他实验中， 将研究异常皮质的第V层内，以确定 轴突发芽导致异常的功能性兴奋性连接。 所采用的技术将包括免疫细胞化学、全细胞记录、免疫细胞化学和免疫细胞化学。 皮层神经元的电流和电位，最小刺激和 应用扫描激光光解笼状谷氨酸。结果 与脑外伤后癫痫的发病机制有关。的 长期目标是利用这些信息找到预防战略， 创伤后癫痫