ELECTROPHYSIOLOGY OF DENTATE GYRUS

齿状回的电生理学

• 批准号: 3478437
• 负责人: ANNE WILLIAMSON
• 金额: $ 9.38万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1996-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3478437
• 关键词: GABA receptor; NMDA receptors; acidity /alkalinity; biopsy; brain cell; calcium flux; cell cell interaction; dentate gyrus; dyes; dynorphins; electrophysiology; epilepsy; extracellular; glycine receptors; guinea pigs; human tissue; inhibitor /antagonist; interneurons; laboratory rat; magnesium; membrane potentials; microelectrodes; neuropeptide Y; sclerosis; somatostatin; stainings; temporal lobe /cortex disorder; voltage /patch clamp; zinc

The dentate gyrus provides the primary input to the hippocampus proper via the perforant path and has been implicated in the pathogenesis of certain types of human and animal epilepsy. However, the electrophysiological characteristics of the cells found in this region are poorly understood. This proposal is designed to examine the electrophysiological properties of cells from human and rodent dentate gyri. The human tissue used in this study is biopsy tissue from patients with medically intractable epilepsy and falls into two categories: those with medial temporal lobe sclerosis in which a number of biochemical and histological markers in the hippocampus are affected, and those with lesions or tumors in the temporal lobe in which these markers are relatively unaffected. All the experiments outlined below will be performed in parallel in rodent tissue. The hippocampi are maintained as 400 micrometer slices in an in vitro recording chamber and electrophysiological recording and cell labelling techniques will be used. The broad goals of this project are to determine if specific changes, at the level of single cells, can be seen in epileptic tissue relative to the comparison human tissue and to rodent controls. Our specific goals include: first, to classify the morphological and electrophysiological characteristics of both the granule cells and interneurons found in the dentate for the two types of human tissue as well as for rodents; second, to study the exciatory and inhibitory properties and their modulation in these three types of tissue and third to assess the actions of a number of peptide neurotransmitters which are affected in cases of temporal lobe sclerosis. A significant portion of this proposal is devoted to studying the modulation of the NMDA type glutamate receptor in the three classes of tissue. This receptor appears to underlie epileptiform activity in a number of animal epilepsy models and thus changes in the modulation of this receptor subtype are candidates for the hyperexcitability seen in the sclerotic tissue. Three modulators will be examined in detail: extracellular pH, Zn, and Mg.

齿状回通过以下方式向海马体提供主要输入： 穿通路径并与某些疾病的发病机制有关 人类和动物癫痫的类型。 然而，电生理学 人们对该区域发现的细胞的特征知之甚少。 该提案旨在检查电生理特性 来自人类和啮齿动物齿状回的细胞。 本实验中使用的人体组织 研究对象是难治性癫痫患者的活检组织 分为两类：患有内侧颞叶硬化的人 海马体中有许多生化和组织学标志物 受到影响，以及那些在颞叶有病变或肿瘤的人 这些标记相对不受影响。 所有的实验 下面概述的将在啮齿动物组织中并行进行。 这 在体外记录中海马体保持为 400 微米切片 室和电生理记录以及细胞标记技术 将被使用。 该项目的总体目标是确定具体的变化是否在 单细胞的水平，可以在癫痫组织中看到 比较人体组织和啮齿动物对照。 我们的具体目标 包括：第一，形态学和电生理学分类 颗粒细胞和中间神经元的特征 两种类型的人体组织以及啮齿动物均具有齿状；第二， 研究兴奋性和抑制性及其调节 这三种类型的组织，第三是评估一些组织的行动 颞叶受影响的肽神经递质 硬化。 该提案的很大一部分致力于研究 NMDA 型谷氨酸受体的三类调节 组织。 该受体似乎是癫痫样活动的基础 动物癫痫模型的数量以及这种调节的变化 受体亚型是在 硬化组织。 将详细检查三个调制器： 细胞外 pH、锌和镁。