NEURONS AND GLIA IN VITRO

影响启动和停止的生理因素 皮层癫痫放电对于理解 这个过程的病理生理学。 细胞外离子浓度 大脑影响神经元的行为，可以作为调节剂， 癫痫放电;事实上，这已经被证明是这种情况， 细胞外[K+]。 细胞外pH值（pHo）最近已被证明 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; 具体地，酸位移降低兴奋性并阻断NMDA电流。 此外，pH值的大而持久的变化发生在强烈的 神经活动 活性依赖性pHo向酸性方向移动 似乎至少部分由神经胶质细胞介导。 这些 观察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，介导的 部分由神经胶质细胞，作为一种负反馈机制， 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微电极。 的作用 神经胶质细胞介导细胞外酸化将研究使用 离子敏感微电极和“纯胶质”大鼠视神经。 细胞内pH调节方面可能有助于 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。 这项研究代表了一个 继续研究哺乳动物的基本生理特性 神经胶质细胞与脑离子和容量调节的关系 细胞外间隙 这些研究将提供有用的新资料 关于大脑中pH值波动的机制，同时评估 pHo作为过度神经活动的调节剂的重要性， 癫痫

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.