THALAMOCORTICAL NEURON DYNAMICS AND ABSENCE EPILEPSY

丘脑皮质神经元动力学与失神性癫痫

• 批准号: 2270191
• 负责人: William W Lytton
• 金额: $ 8.97万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-14 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2270191
• 关键词: action potentials; brain electrical activity; computational neuroscience; computer system hardware; dendrites; electrical potential; epilepsy; membrane channels; membrane potentials; neuroanatomy; neurophysiology; potassium channel; sodium channel; synapses; thalamocortical tract; thalamus; voltage gated channel

Understanding absence epilepsy will require understanding thalamic oscillations. The long term goal of this research is to use computer models to integrate known details of intrinsic neuronal properties and synaptic inputs to explain the genesis of the physiological and pathological slow rhythms of the thalamus. Intrinsic cell dynamics and synaptic connectivity interact in complex ways. Models of individual brain areas can provide a framework for integrating new physiological and pharmacological observations. A complement to animal models of epilepsy, computer models have the flexibility to extensively explore complex neuronal interactions that may suggest new pharmacological approaches. Slow oscillations in the thalamus, in both the 3 Hz range of absence epilepsy and slow-wave sleep in the 10 Hz range of sleep spindles, appear to involve low-threshold calcium spikes due to the T-type calcium channel (T channel). Ethosuximide, an anticonvulsant used for absence epilepsy, alters the kinetics of this channel. Computer modeling will be used 1) to determine the effects of passive properties and dendritic ion channels on the integrative properties of the neurons, 2) to relate neuronal firing patterns to the density and kinetics of ion channels, 3) to evaluate how physiological and pharmacological modulation of ion channels might alter the intrinsic oscillations of thalamocortical neurons, 4) to explore how repetitive intracellular stimulation or repetitive cortical synaptic input would affect oscillatory patterns, 5) to evaluate the contribution of intrinsic versus network properties in synchronizing slow oscillations in networks of simplified model neurons.

了解缺席癫痫将需要了解丘脑 振荡。 这项研究的长期目标是使用计算机 集成了内在神经元特性的已知细节和 突触输入来解释生理和 丘脑的病理慢节奏。 固有的细胞动力学和 突触连通性以复杂的方式相互作用。 个体的模型 大脑区域可以提供一个框架，以整合新的生理和 药理观察。 对癫痫动物模型的补充， 计算机模型具有广泛探索复合物的灵活性 神经元相互作用可能暗示了新的药理方法。 在丘脑中的缓慢振荡，在3 Hz的缺失范围内 癫痫和慢波睡眠在10 Hz范围的睡眠纺锤范围内出现，出现 涉及由于T型钙通道引起的低阈值钙尖峰 （t通道）。 Ethosuximide，一种用于缺有癫痫的抗惊厥药， 改变了此频道的动力学。 计算机建模将使用1） 确定被动特性和树突离子通道的影响 关于神经元的综合特性，2）与神经元相关 向离子通道的密度和动力学发射模式，3） 评估离子通道的生理和药理调节方式 可能会改变丘脑皮质神经元的固有振荡，4） 探索重复的细胞内刺激或重复性皮质 突触输入将影响振荡模式，5）评估 内在与网络属性在同步慢速方面的贡献 简化模型神经元网络中的振荡。