CELLULAR EPILEPTIC MECHANISMS

细胞癫痫机制

• 批准号: 3404747
• 负责人: WAYNE E. CRILL
• 金额: $ 6.96万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404747
• 关键词: brain cell; brain electrical activity; cellular pathology; cerebral cortex; electrophysiology; electrostimulus; evoked potentials; membrane structure; neuropharmacology; nontherapeutic iontophoresis; partial seizure; potassium; synapses

With this proposal we request funds to continue our studies of epileptic mechanisms in the mammalian central nervous system. It has been known for many years that focal epileptic behavior is characterized by a synchronized discharge of cortical neurons and that this activity can spread throughout normal cortex. Our objective is to perform experiments that will clarify the mechanisms whereby normal neuronal circuits become involved in the epileptic process. This work will examine both the excitable properties of individual neurons and synaptic mechanisms. We will study in anesthetized cats the normal behavior of layer V nerurons and the response of these neurons to repetitive cortical stimulation to evoke seizure discharges using intracellular recording and the single electrode voltage clamp (SEVC). We are interested in the change in subthreshold ionic currents during the evolution of epileptic behavior in normal neurons. Experiments are proposed that will allow us to distinguish synaptic mechanisms from alterations in neuron excitability. Moreover, these experiments will allow us to validate our experiments in the in vitro cortical slice preparation. A second aim of this proposal is to use the neocortical slice to study in more detail the effects of graded changes in intracellular potassium concentration and the effects of synchronized electrical stimulation on the subthreshold currents of larger layer V neurons. We will also be able to test in more detail hypotheses about underlying mechanisms derived from the in vivo experiments. These experiments should add a significant piece of information to our understanding of the pathophysiologic mechanisms for focal epilepsy.

通过此提案，我们要求资金继续我们的癫痫病研究 哺乳动物中枢神经系统中的机制。 它以 局灶性癫痫行为以同步为特征的多年 皮质神经元的排放，并且该活动可以扩散到整个 正常皮质。 我们的目标是进行实验，以澄清 正常神经元电路参与的机制 癫痫工艺。 这项工作将检查既有的兴奋性能 单个神经元和突触机制。 我们将麻醉 猫的正常行为v nerurons及其响应 神经元重复皮质刺激以引起癫痫发作 使用细胞内记录和单电极电压夹 （SEVC）。 我们对亚阈值离子电流的变化感兴趣 在正常神经元中癫痫行为的演变过程中。 实验 提出了使我们能够区分突触机制的 神经元兴奋性的改变。 而且，这些实验将允许 我们在体外皮质切片制备中验证我们的实验。 该提议的第二个目的是使用新皮质切片来研究 更多详细说明细胞内钾的分级变化的影响 浓度和同步电刺激对 较大层V神经元的子阈值电流。 我们还将能够 更详细地测试有关从该机制得出的基本机制的假设 体内实验。 这些实验应添加重要的一部分 信息以了解我们对病理生理机制的理解 局灶性癫痫。