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.

计算机模拟的电生理行为 通过细胞外钾离子（K+）相互作用的神经元素 共享细胞外空间中的浓度变化已有 发达。 拟议项目的目的是整合电流 这些活动依赖于K+的实验数据 具有预测方案的变化，以探索其潜力 功能意义。 离子耦合之间的通用性 将研究中枢神经系统的活性和非活性细胞元素 通过建模特定的区域几何形状。 要考虑的是： （1）这种耦合可能对发射稳定性产生的影响 相邻神经元的模式，（2）K+介导的去极化为A 经典化学神经传递的突触前调节剂（3） 活性依赖性离子梯度变化作为局部非特异性 密集单元组件中的信号传导参数和（4）应用 这些概念是神经中​​正式学习模型的概念 “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） 神经胶质和神经膜在该地区的相对分布， （3）驱动的程度（外部或自发固有） 神经活动和（4）重合程度（同步性） 邻居附近驱动的AP活动。 结果将是 扩展到包含跨膜的动态变化 其他相关离子的梯度（Na+，Ca+，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介导的离子耦合具有 关于不稳定性和癫痫样活动的影响 在神经网络中，主要的概念应用将是 一般信息处理。 动力学的新颖性 居住在一个事实中，除了固定的结构突触外 相互作用，限制环境的细胞可以通过 从几何意义上讲，它们的接近性 外源驾驶的同步性使活动痕迹 由细胞外钾瞬变提供的 局部神经元整合的基础。 这个理论 调查将有助于考虑小规模 与当前技术抗拒研究的合作互动 但可能被认为在功能信息中发挥作用 在离散的CNS环境中进行处理。