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用于模拟异质性新皮层锥体细胞群体的实验验证参数集

Experimentally Verified Parameter Sets for Modelling Heterogeneous Neocortical Pyramidal-Cell Populations.

作者信息

Harrison Paul M, Badel Laurent, Wall Mark J, Richardson Magnus J E

机构信息

MOAC Doctoral Training Centre, University of Warwick, Coventry, United Kingdom; School of Life Sciences, University of Warwick, Coventry, United Kingdom; Warwick Systems Biology Centre, University of Warwick, Coventry, United Kingdom.

Laboratory for Circuit Mechanisms of Sensory Perception, RIKEN Brain Science Institute, Wako, Saitama, Japan.

出版信息

PLoS Comput Biol. 2015 Aug 20;11(8):e1004165. doi: 10.1371/journal.pcbi.1004165. eCollection 2015 Aug.

Abstract

Models of neocortical networks are increasingly including the diversity of excitatory and inhibitory neuronal classes. Significant variability in cellular properties are also seen within a nominal neuronal class and this heterogeneity can be expected to influence the population response and information processing in networks. Recent studies have examined the population and network effects of variability in a particular neuronal parameter with some plausibly chosen distribution. However, the empirical variability and covariance seen across multiple parameters are rarely included, partly due to the lack of data on parameter correlations in forms convenient for model construction. To addess this we quantify the heterogeneity within and between the neocortical pyramidal-cell classes in layers 2/3, 4, and the slender-tufted and thick-tufted pyramidal cells of layer 5 using a combination of intracellular recordings, single-neuron modelling and statistical analyses. From the response to both square-pulse and naturalistic fluctuating stimuli, we examined the class-dependent variance and covariance of electrophysiological parameters and identify the role of the h current in generating parameter correlations. A byproduct of the dynamic I-V method we employed is the straightforward extraction of reduced neuron models from experiment. Empirically these models took the refractory exponential integrate-and-fire form and provide an accurate fit to the perisomatic voltage responses of the diverse pyramidal-cell populations when the class-dependent statistics of the model parameters were respected. By quantifying the parameter statistics we obtained an algorithm which generates populations of model neurons, for each of the four pyramidal-cell classes, that adhere to experimentally observed marginal distributions and parameter correlations. As well as providing this tool, which we hope will be of use for exploring the effects of heterogeneity in neocortical networks, we also provide the code for the dynamic I-V method and make the full electrophysiological data set available.

摘要

新皮质网络模型越来越多地纳入兴奋性和抑制性神经元类别的多样性。在一个标称神经元类别中,细胞特性也存在显著变异性,并且可以预期这种异质性会影响网络中的群体反应和信息处理。最近的研究已经考察了具有一些合理选择分布的特定神经元参数变异性的群体和网络效应。然而,多个参数之间的经验变异性和协方差很少被纳入,部分原因是缺乏便于模型构建的参数相关性数据。为了解决这个问题,我们结合细胞内记录、单神经元建模和统计分析,对第2/3层、第4层以及第5层的细长簇状和粗簇状锥体细胞中的新皮质锥体细胞类别内部和之间的异质性进行了量化。从对方波脉冲和自然波动刺激的反应中,我们研究了电生理参数的类别依赖性方差和协方差,并确定了h电流在产生参数相关性中的作用。我们采用的动态I-V方法的一个副产品是从实验中直接提取简化的神经元模型。从经验上看,这些模型采用了不应期指数积分发放形式,并且当尊重模型参数的类别依赖性统计时,能够准确拟合不同锥体细胞群体的胞体周围电压反应。通过量化参数统计,我们获得了一种算法,该算法为四个锥体细胞类别中的每一个生成符合实验观察到的边缘分布和参数相关性的模型神经元群体。除了提供这个我们希望将用于探索新皮质网络异质性影响的工具外,我们还提供了动态I-V方法的代码,并提供完整的电生理数据集。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9b9/4546387/086fa6dbc151/pcbi.1004165.g001.jpg

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