NEURONS AND GLIA IN VITRO

体外神经元和神经胶质细胞

• 批准号: 3396360
• 负责人: BRUCE Robert RANSOM
• 金额: $ 25.63万
• 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/3396360
• 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.

影响开始和停止的生理因素 皮质癫痫放电对于理解 这个过程的病理生理学。 细胞外离子浓度 大脑影响神经元行为并可以作为调节器 癫痫放电；事实上，这已被证明是这种情况 细胞外[K+]。 细胞外 pH (pHo) 最近被证明可以 直接影响神经元的兴奋性并调节 N-甲基 D-天冬氨酸 (NMDA) 受体的兴奋性神经递质； 具体来说，酸移会降低兴奋性并阻断 NMDA 电流。 此外，pHo 会随着强烈的变化而发生大而持久的变化。 神经活动。 活性依赖性 pHo 向酸方向移动 似乎至少部分是由神经胶质细胞介导的。 这些 观察结果提示癫痫放电受到影响的假设 通过 pHo 和活性依赖性细胞外酸化，介导 部分由神经胶质细胞组成，作为负反馈机制抑制 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微电极。 的作用 将使用以下方法研究神经胶质细胞介导细胞外酸化的作用 离子敏感微电极和“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 将在培养的神经胶质细胞中分析细胞外酸化 神经元使用显微荧光测定法。 拟议的研究代表了 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 评估大脑中 pHo 波动的机制 pHo 作为过度神经活动调节剂的重要性 癫痫。