POTASSIUM-MEDIATED IONIC COUPLING IN CNS--COMPUTER MODEL

中枢神经系统中钾介导的离子偶联--计算机模型

• 批准号: 3413015
• 负责人: ROBERT M. LEBOVITZ
• 金额: $ 6.15万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3413015
• 关键词: action potentials; biological signal transduction; calcium channel; central nervous system; computer graphics /printing; computer program /software; computer simulation; electrophysiology; extracellular matrix; glia; ion transport; mathematical model; membrane model; membrane permeability; membrane potentials; neural information processing; neural transmission; neurons; neurophysiology; neurotransmitters; potassium channel; sodium channel; synapses

A computer simulation of the electrophysiological behavior of neural elements interacting via extracellular potassium ion (K+) concentration variations in a shared extracellular space has been developed. The aim of the proposed project is to integrate current experimental data that characterize these activity dependent K+ variations with a predictive scheme for exploring their potential functional significance. The generality of ionic coupling between active and inactive cellular elements of the CNS will be studied by modeling particular regional geometries. To be considered are: (1) the effects that such coupling may have on stability of firing patterns of adjacent neurons, (2) K+-mediated depolarization as a presynaptic modulator of classic chemical neurotransmission, (3) activity-dependent ion gradient variations as a locally nonspecific signaling parameter in dense cell assemblies and (4) application of these concepts to formalized models of learning in neural "networks". The physiological variables to be explored are (1) the width and local geometry of the extracellular environment, (2) the relative distribution of glial and neural membrane in that locale, (3) the degree of driven (extrinsic or spontaneous intrinsic) neural activity, and (4) the degree of coincidence (synchronicity) of driven AP activity among near neighbors. The results will be extended to include dynamic variations in the transmembrane gradients of other relevant ions (Na+, Ca+, and to explore the relation of the above concepts to pathologic states, such as epileptiform activity. Although k-mediated ionic-coupling has implications with respect to instability and epileptiform activity in neural networks, a major conceptual application will be to information processing in general. The novelty of the dynamics resides in the fact that in addition to fixed structural synaptic interactions, the cells of a circumscribed locale may be linked by their proximity in a geometric sense and by the relative synchronicity of exogenous driving such that the traces of activity that are provided by extracellular potassium transients becomes a basis for local neuronal integration. This theoretical investigation will facilitate consideration of small scale cooperative interactions that resist study with current techniques but may be considered to play a role in functional information processing in discrete CNS locales.

电生理行为的计算机模拟 通过细胞外钾离子 (K+) 相互作用的神经元件 共享细胞外空间的浓度变化 发达。 拟议项目的目的是整合当前的 表征这些活性依赖性 K+ 的实验数据 与探索其潜力的预测方案的变化 功能意义。 离子间耦合的一般性 将研究中枢神经系统的活性和非活性细胞元件 通过对特定区域的几何形状进行建模。 需要考虑的是： (1)这种耦合对射击稳定性可能产生的影响 相邻神经元的模式，（2）K+介导的去极化作为 经典化学神经传递的突触前调节剂，(3) 依赖于活性的离子梯度变化作为局部非特异性 致密细胞集合体中的信号参数及(4)应用 将这些概念转化为神经学习的形式化模型 “网络”。 要探索的生理变量是（1） 细胞外环境的宽度和局部几何形状，（2） 该区域神经胶质和神经膜的相对分布， (3) 驱动程度（外在或自发内在） 神经活动，以及（4）重合程度（同步性） 近邻之间驱动的 AP 活动。 结果将是 扩展到包括跨膜的动态变化 其他相关离子（Na+、Ca+）的梯度，并探索 上述概念与病理状态的关系，例如 癫痫样活动。 尽管 k 介导的离子耦合 对不稳定和癫痫样活动的影响 在神经网络中，一个主要的概念应用是 一般信息处理。 动态的新颖性 事实在于，除了固定的结构突触之外 相互作用，限制区域的细胞可以通过以下方式连接 它们在几何意义上的接近和相对 外源驱动的同步性使得活动的痕迹 由细胞外钾瞬变提供的 局部神经元整合的基础。 这个理论上的 调查将有助于考虑小规模 合作互动阻碍了现有技术的研究 但可能被认为在功能信息中发挥作用 在离散的 CNS 区域中进行处理。