THALAMOCORTICAL NEURON DYNAMICS AND ABSENCE EPILEPSY

了解失神癫痫需要了解丘脑 振荡 这项研究的长期目标是利用计算机 模型整合内在神经元特性的已知细节， 突触输入来解释生理和 丘脑的病态缓慢节奏 内在细胞动力学和 突触连接以复杂的方式相互作用。 个人模型 大脑区域可以提供一个框架， 药理学观察 癫痫动物模型的补充， 计算机模型具有广泛探索复杂 神经元的相互作用，这可能表明新的药理学方法。 缓慢的振荡在丘脑，在这两个3赫兹范围内的缺席 癫痫和慢波睡眠在10赫兹范围内的睡眠纺锤波，出现 涉及T型钙通道引起的低阈值钙峰 （T通道）。 乙琥胺，一种用于失神癫痫的抗惊厥药， 改变了这个通道的动力学。 将使用计算机建模1） 以确定被动特性和树枝状离子通道的影响， 对神经元的整合特性，2）将神经元 发射模式与离子通道的密度和动力学有关，3） 评价离子通道的生理和药理学调节 可能改变丘脑皮层神经元的内在振荡，4） 探索重复的细胞内刺激或重复的皮层刺激 突触输入会影响振荡模式，5）以评估 内在特性与网络特性在同步缓慢中的作用 简化模型神经元网络中的振荡。

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.