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首页> 外文期刊>Frontiers in Computational Neuroscience >Homologous Basal Ganglia Network Models in Physiological and Parkinsonian Conditions
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Homologous Basal Ganglia Network Models in Physiological and Parkinsonian Conditions

机译:生理和帕金森病条件下的同源基底神经节网络模型

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The classical model of basal ganglia has been refined in recent years with discoveries of subpopulations within a nucleus and previously unknown projections. One such discovery is the presence of subpopulations of arkypallidal and prototypical neurons in external globus pallidus, which was previously considered to be a primarily homogeneous nucleus. Developing a computational model of these multiple interconnected nuclei is challenging, because the strengths of the connections are largely unknown. We therefore use a genetic algorithm to search for the unknown connectivity parameters in a firing rate model. We apply a binary cost function derived from empirical firing rate and phase relationship data for the physiological and Parkinsonian conditions. Our approach generates ensembles of over 1,000 configurations, or homologies, for each condition, with broad distributions for many of the parameter values and overlap between the two conditions. However, the resulting effective weights of connections from or to prototypical and arkypallidal neurons are consistent with the experimental data. We investigate the significance of the weight variability by manipulating the parameters individually and cumulatively, and conclude that the correlation observed between the parameters is necessary for generating the dynamics of the two conditions. We then investigate the response of the networks to a transient cortical stimulus, and demonstrate that networks classified as physiological effectively suppress activity in the internal globus pallidus, and are not susceptible to oscillations, whereas parkinsonian networks show the opposite tendency. Thus, we conclude that the rates and phase relationships observed in the globus pallidus are predictive of experimentally observed higher level dynamical features of the physiological and parkinsonian basal ganglia, and that the multiplicity of solutions generated by our method may well be indicative of a natural diversity in basal ganglia networks. We propose that our approach of generating and analyzing an ensemble of multiple solutions to an underdetermined network model provides greater confidence in its predictions than those derived from a unique solution, and that projecting such homologous networks on a lower dimensional space of sensibly chosen dynamical features gives a better chance than a purely structural analysis at understanding complex pathologies such as Parkinson's disease.
机译:近年来,随着神经核内亚群的发现和以前未知的预测,对基底节的经典模型进行了改进。这样的发现之一是在外部苍白球(先前被认为是主要的同质核)中存在苍白球和原型神经元的亚群。由于连接的强度很大程度上未知,因此开发这些多重互连核的计算模型具有挑战性。因此,我们使用遗传算法在点火速率模型中搜索未知的连通性参数。我们应用从经验放电率和相位关系数据得出的生理和帕金森病条件下的二元成本函数。我们的方法为每种条件生成超过1,000种配置或同调的合奏,其中许多参数值具有广泛的分布,并且两个条件之间存在重叠。但是,从原型神经元到睑板神经元的连接的有效权重与实验数据一致。我们通过分别和累积地操纵参数来研究权重变化的重要性,并得出结论,参数之间观察到的相关性对于生成两个条件的动力学是必要的。然后,我们调查了网络对瞬态皮质刺激的反应,并证明被归类为生理网络有效抑制了苍白球内部的活动,并且不易振荡,而帕金森氏网络则显示出相反的趋势。因此,我们得出结论,在苍白球中观察到的速率和相位关系可以预示实验观察到的生理性和帕金森氏基底神经节的更高水平的动力学特征,并且通过我们的方法产生的溶液的多样性很可能表明自然多样性在基底神经节网络中。我们建议,对于未确定的网络模型,我们生成和分析多个解决方案集合的方法比从唯一的解决方案得出的预测更具信心,并且将此类同源网络投影在合理选择的动态特征的较低维空间上,可以提供在理解复杂的病理学(例如帕金森氏病)方面,比单纯的结构分析更好的机会。

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