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.

齿状回为正常的海马提供了主要输入 穿孔路径，与某些发病机理有关 人类和动物癫痫的类型。 但是，电生理学 在该区域发现的细胞的特征知之甚少。 该建议旨在检查 来自人类和啮齿动物齿状回的细胞。 在此使用的人体组织 研究是来自医学上顽固性癫痫患者的活检组织 并分为两类：那些有内侧颞叶硬化症的类别 海马中的许多生化和组织学标记 受到影响，颞叶中有病变或肿瘤的人 这些标记相对不受影响。 所有实验 下面概述的将在啮齿动物组织中并联进行。 这 海马在体外记录中保持为400千分尺 腔室和电生理记录和细胞标记技术 将使用。 该项目的广泛目标是确定特定的更改是否在 单个细胞的水平相对于癫痫组织可以看到 比较人体组织和啮齿动物对照。 我们的具体目标 包括：首先，对形态学和电生理学进行分类 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的齿状；第二， 研究探究性和抑制性能及其在 这三种类型的组织和第三类，以评估许多 在颞叶病例中受到影响的肽神经递质 硬化。 该提案的很大一部分致力于研究 NMDA型谷氨酸受体在三类中调节 组织。 该受体似乎是在A中的癫痫表现的基础 动物癫痫模型的数量，因此调制的变化 受体亚型是候选者的过度兴奋性 硬化组织。 将详细检查三个调节器： 细胞外pH，Zn和mg。