ELECTROPHYSIOLOGY OF DENTATE GYRUS

齿状回为海马体本身提供初级输入，通过 穿孔路径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 人们对这一区域发现的细胞的特征知之甚少。 这项建议是为了检查电生理特性 来自人类和啮齿动物齿状回的细胞。在这个过程中使用的人体组织 研究是来自药物难治性癫痫患者的活检组织。 并分为两类：内侧颞叶硬化症患者 海马体中的一些生化和组织学标志物 是受影响的，而那些在颞叶有损伤或肿瘤的人 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执行。这个 在体外记录中，海马体被保持为400微米的切片 小室和电生理记录及细胞标记技术 将会被使用。 该项目的总体目标是确定具体的变化是否在 单个细胞的水平，可以在癫痫组织中看到相对于 将人体组织与啮齿动物对照组进行比较。我们的具体目标 包括：第一，对形态和电生理进行分类 大鼠脑内颗粒细胞和中间神经元的特征 对于这两种类型的人类组织以及啮齿动物；第二， 研究神经递质的兴奋性和抑制性及其调控 这三种类型的组织和第三种评估的行动 影响颞叶病变的多肽类神经递质 硬化症。这份提案的很大一部分是用来研究 NMDA型谷氨酸受体在三类神经细胞中的调节作用 组织。这种受体似乎是癫痫样活动的基础 动物癫痫模型的数量及其在这一调节中的变化 受体亚型是可见的过度兴奋的候选 硬化性组织。我们将详细研究三种调制器： 胞外pH、锌和镁。

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.