DENDRITIC MECHANISMS OF EPILEPSY

癫痫的树突状机制

• 批准号: 3406142
• 负责人: LEONA M MASUKAWA
• 金额: $ 7.28万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3406142
• 关键词: action potentials; anticonvulsants; calcium channel blockers; convulsants; dendrites; electrophysiology; epilepsy; hippocampus; membrane permeability; neuroanatomy; neurons; neuropharmacology; neurophysiology; oxygen microelectrode

The objective of this proposal is to understand the dendritic mechanisms that underlie normal and seizure states of the brain. In order to attain this objective, it is first necessary to analyze the multiple factors (e.g., synaptic and non-synaptic membrane conductances) that interact to influence neuronal excitability. Because the hippocampus is involved in important forms of abnormal discharges, both generalized and focal epilepsy, the electrical responses of hippocampal neurons will be studied using intracellular volatge recordings in the slice preparation. Very little is known about dendritic electrical properties and how they are involved in epileptic seizure discharges, although the central role of dendrites in neuronal excitability is well accepted. Therefore, it is the primary aim of this proposal to systematically analyze the non-synaptic ion specific conductances of dendrites. For this purpose we will use a novel preparation involving intradendritic recordings from physically isolated dendrites in the hippocampus. This preparation will allow more precise analysis of dendritic electrical events than previous conventional recordings from the cell body. In conjunction with this study, I will use specific channel blocking agents to test the hypothesis that potassium-dependent properties of the dendrite play a crucial role in controlling neuronal discharge. I will further test the hypothesis that convulsant and clinically relevant anticonvulsant agents have their effects by acting primarily on these dendritic properties. These studies therefore are important for a complete understanding of dendritic function in neuronal excitability.

该提议的目的是了解树突状机制 这是大脑正常和癫痫发作状态的基础。 为了达到 这个目标，首先需要分析多种因素 （例如，突触和非突触膜电导）与 影响神经元兴奋性。 因为海马参与 普遍和焦点的重要形式的异常排放 癫痫病，将研究海马神经元的电反应 在切片制备中使用细胞内伏特记录。 非常 关于树突电性能及其如何，知之甚少 涉及癫痫发作的排放，尽管 神经元兴奋性中的树突被公认。 因此，是 该建议的主要目的是系统地分析非突触离子 树突的特定电导。 为此目的，我们将使用小说 涉及物理隔离的内端记录的准备 海马中的树突。 这种准备将允许更精确 与以前的常规事件分析树突电气事件 来自细胞体的记录。 结合这项研究，我将使用 特定的通道阻塞剂以检验以下假设 树突的钾依赖性特性在 控制神经元放电。 我将进一步检验以下假设 抽搐和临床相关的抗惊厥药具有其作用 通过主要作用于这些树突特性。 因此，这些研究 对于完全了解树突状功能很重要 神经元兴奋性。