Institute of Neuroinformatics, University and ETH Zurich, Zurich, Switzerland.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America.
PLoS Comput Biol. 2020 Feb 13;16(2):e1007315. doi: 10.1371/journal.pcbi.1007315. eCollection 2020 Feb.
Axonal morphology displays large variability and complexity, yet the canonical regularities of the cortex suggest that such wiring is based on the repeated initiation of a small set of genetically encoded rules. Extracting underlying developmental principles can hence shed light on what genetically encoded instructions must be available during cortical development. Within a generative model, we investigate growth rules for axonal branching patterns in cat area 17, originating from the lateral geniculate nucleus of the thalamus. This target area of synaptic connections is characterized by extensive ramifications and a high bouton density, characteristics thought to preserve the spatial resolution of receptive fields and to enable connections for the ocular dominance columns. We compare individual and global statistics, such as a newly introduced length-weighted asymmetry index and the global segment-length distribution, of generated and biological branching patterns as the benchmark for growth rules. We show that the proposed model surpasses the statistical accuracy of the Galton-Watson model, which is the most commonly employed model for biological growth processes. In contrast to the Galton-Watson model, our model can recreate the log-normal segment-length distribution of the experimental dataset and is considerably more accurate in recreating individual axonal morphologies. To provide a biophysical interpretation for statistical quantifications of the axonal branching patterns, the generative model is ported into the physically accurate simulation framework of Cx3D. In this 3D simulation environment we demonstrate how the proposed growth process can be formulated as an interactive process between genetic growth rules and chemical cues in the local environment.
轴突形态表现出很大的可变性和复杂性,但皮层的典型规律表明,这种布线是基于一小部分遗传编码规则的重复启动。因此,提取潜在的发育原则可以揭示在皮层发育过程中必须有哪些遗传编码指令。在生成模型中,我们研究了来自丘脑外侧膝状体核的猫区 17 中的轴突分支模式的生长规则。这个突触连接的目标区域具有广泛的分支和高的突触及密度,这些特征被认为可以保留感受野的空间分辨率,并为眼优势柱提供连接。我们将生成的和生物学分支模式的个体和全局统计数据进行比较,例如新引入的长度加权不对称指数和全局分段长度分布,作为生长规则的基准。我们表明,所提出的模型超过了最常用于生物生长过程的 Galton-Watson 模型的统计精度。与 Galton-Watson 模型不同,我们的模型可以重现实验数据集的对数正态分段长度分布,并且在重现个体轴突形态方面要准确得多。为了为轴突分支模式的统计量化提供生物物理解释,生成模型被移植到 Cx3D 的物理准确模拟框架中。在这个 3D 模拟环境中,我们演示了如何将所提出的生长过程表述为遗传生长规则和局部环境中化学线索之间的交互过程。