NEURONS AND GLIA IN VITRO

体外神经元和神经胶质细胞

• 批准号: 3396361
• 负责人: BRUCE Robert RANSOM
• 金额: $ 26.02万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396361
• 关键词: NMDA receptors; acid base balance; astrocytes; barium; brain electrical activity; carbon dioxide tension; cerebral cortex; confocal scanning microscopy; electrophysiology; epilepsy; extracellular; fluorescent dye /probe; glia; hippocampus; ions; laboratory rat; microelectrodes; neurons; neurophysiology; optic nerve; oxygen tension; potassium; tissue /cell culture

Physiological factors which influence the initiation and cessation of cortical epileptic discharge are important in understanding the pathophysiology of this process. Extracellular ion concentrations in the brain influence neuronal behavior and could serve as modulators of epileptic discharge; in fact, this has been shown to be the case for extracellular [K+]. Extracellular pH (pHo) has recently been shown to directly influence neuronal excitability and to modulate the action of excitatory neurotransmitters at the N-methyl D-Aspartate (NMDA) receptor; specifically, acid shifts decrease excitability and block NMDA currents. Furthermore, large and long-lasting changes in pHo occur with intense neural activity. Activity-dependent pHo shifts in the acid direction appear to be mediated, at least in part, by glial cells. These observations prompt the hypotheses that epileptic discharge is influenced by pHo and that activity-dependent extracellular acidification, mediated in part by glial cells, acts as a negative feedback mechanism to inhibit epileptic discharge. These hypotheses will be tested using neocortical and hippocampal brain slices and ion-sensitive microelectrodes. The role of glial cells in mediating extracellular acidification will be studied using ion-sensitive microelectrodes and the 'pure glial' rat optic nerve. Aspects of intracellular pH regulation that might contribute to extracellular acidification will be analyzed in cultured glial cells and neurons using microfluorometry. The proposed research represents a continuation of studies on the basic physiological properties of mammalian glial cells, in relationship to the ionic and volume regulation of brain extracellular space. These studies will provide useful new information about the mechanisms of pHo fluctuations in the brain while assessing the importance of pHo as a modulator of the excessive neural activity seen in epilepsy.

影响启动和停止的生理因素 皮质癫痫放电对于理解 该过程的病理生理学。 细胞外离子浓度 大脑会影响神经元行为，并可以作为调节剂 癫痫排放；实际上，事实证明 细胞外[K+]。 细胞外pH（PHO）最近已显示为 直接影响神经元兴奋性并调节 N-甲基D-天冬氨酸（NMDA）受体的兴奋性神经递质； 具体而言，酸移位可降低兴奋性并阻止NMDA电流。 此外，pho的巨大变化发生了强烈的变化 神经活动。 依赖活性的PHO在酸方向上移动 似乎至少部分地是由神经胶质细胞介导的。 这些 观察促使人们假设癫痫排放受到影响 通过phO和活性依赖性的细胞外酸化，介导 部分由神经胶质细胞作为抑制的负反馈机制 癫痫放电。 这些假设将使用新皮质和 海马脑切片和离子敏感的微电极。 的作用 将研究中介导细胞外酸化中的神经胶质细胞 离子敏感的微电极和“纯神经胶质”大鼠视神经。 细胞内pH调节的各个方面可能有助于 细胞外酸化将在培养的神经胶质细胞和 使用微荧光测定法神经元。 拟议的研究代表 继续研究哺乳动物的基本生理特性 神经胶质细胞与大脑的离子和体积调节有关 细胞外空间。 这些研究将提供有用的新信息 关于大脑中pho波动的机制，同时评估 Pho作为过度神经活动的调节剂的重要性 癫痫。