Courant Institute of Mathematical Sciences, New York University, New York, New York, United States of America.
Department of Mathematics, University of Arizona, Tucson, Arizona, United States of America.
PLoS Comput Biol. 2021 Dec 23;17(12):e1009718. doi: 10.1371/journal.pcbi.1009718. eCollection 2021 Dec.
Constraining the many biological parameters that govern cortical dynamics is computationally and conceptually difficult because of the curse of dimensionality. This paper addresses these challenges by proposing (1) a novel data-informed mean-field (MF) approach to efficiently map the parameter space of network models; and (2) an organizing principle for studying parameter space that enables the extraction biologically meaningful relations from this high-dimensional data. We illustrate these ideas using a large-scale network model of the Macaque primary visual cortex. Of the 10-20 model parameters, we identify 7 that are especially poorly constrained, and use the MF algorithm in (1) to discover the firing rate contours in this 7D parameter cube. Defining a "biologically plausible" region to consist of parameters that exhibit spontaneous Excitatory and Inhibitory firing rates compatible with experimental values, we find that this region is a slightly thickened codimension-1 submanifold. An implication of this finding is that while plausible regimes depend sensitively on parameters, they are also robust and flexible provided one compensates appropriately when parameters are varied. Our organizing principle for conceptualizing parameter dependence is to focus on certain 2D parameter planes that govern lateral inhibition: Intersecting these planes with the biologically plausible region leads to very simple geometric structures which, when suitably scaled, have a universal character independent of where the intersections are taken. In addition to elucidating the geometry of the plausible region, this invariance suggests useful approximate scaling relations. Our study offers, for the first time, a complete characterization of the set of all biologically plausible parameters for a detailed cortical model, which has been out of reach due to the high dimensionality of parameter space.
由于维度灾难,约束控制皮质动力学的许多生物学参数在计算和概念上都具有挑战性。本文通过提出(1)一种新颖的数据驱动的平均场(MF)方法,以有效地映射网络模型的参数空间;以及(2)一种用于研究参数空间的组织原则,从这个高维数据中提取具有生物学意义的关系,来应对这些挑战。我们使用猕猴初级视觉皮层的大规模网络模型来说明这些思想。在 10-20 个模型参数中,我们确定了 7 个参数特别难以约束,并且使用(1)中的 MF 算法在这个 7D 参数立方体中发现了点火率轮廓。将“生物学上合理的”区域定义为包含自发兴奋性和抑制性点火率与实验值兼容的参数,我们发现该区域是一个稍微加厚的余维 1 子流形。这一发现的一个含义是,虽然合理的状态对参数非常敏感,但它们也是稳健和灵活的,只要在参数发生变化时适当补偿即可。我们用于概念化参数依赖性的组织原则是关注某些控制横向抑制的二维参数平面:将这些平面与生物学上合理的区域相交会导致非常简单的几何结构,当适当缩放时,这些结构具有与交点位置无关的通用特征。除了阐明合理区域的几何形状外,这种不变性还暗示了有用的近似缩放关系。我们的研究首次为详细皮质模型的所有生物学上合理的参数集提供了完整的特征描述,由于参数空间的高维性,这一直难以实现。