Simpson Hugh D, Goodhill Geoffrey J
Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
Biol Cybern. 2011 Feb;104(1-2):9-29. doi: 10.1007/s00422-011-0417-y. Epub 2011 Feb 22.
A paradigm model system for studying the development of patterned connections in the nervous system is the topographic map formed by retinal axons in the optic tectum/superior colliculus. Starting in the 1970s, a series of computational models have been proposed to explain map development in both normal conditions, and perturbed conditions where the retina and/or tectum/superior colliculus are altered. This stands in contrast to more recent models that have often been simpler than older ones, and tend to address more limited data sets, but include more recent genetic manipulations. The original exploration of many of the early models was one-dimensional and limited by the computational resources of the time. This leaves open the ability of these early models to explain both map development in two dimensions, and the genetic manipulation data that have only appeared more recently. In this article, we show that a two-dimensional and updated version of the XBAM model (eXtended Branch Arrow Model), first proposed in 1982, reproduces a range of surgical map manipulations not yet demonstrated by more modern models. A systematic exploration of the parameter space of this model in two dimensions also reveals richer behavior than that apparent from the original one-dimensional versions. Furthermore, we show that including a specific type of axon-axon interaction can account for the map collapse recently observed when particular receptor levels are genetically manipulated in a subset of retinal ganglion cells. Together these results demonstrate that balancing multiple influences on map development seems to be necessary to explain many biological phenomena in retinotectal map formation, and suggest important constraints on the underlying biological variables.
用于研究神经系统中模式化连接发育的一个范式模型系统是视网膜轴突在视顶盖/上丘形成的拓扑图。从20世纪70年代开始,人们提出了一系列计算模型来解释正常情况下以及视网膜和/或视顶盖/上丘发生改变的扰动情况下的图谱发育。这与最近的模型形成对比,最近的模型通常比旧模型更简单,倾向于处理更有限的数据集,但包含更新的基因操作。许多早期模型的最初探索是一维的,并且受当时计算资源的限制。这使得这些早期模型能否解释二维图谱发育以及最近才出现的基因操作数据存在疑问。在本文中,我们表明,1982年首次提出的XBAM模型(扩展分支箭头模型)的二维更新版本能够重现一系列现代模型尚未展示的手术图谱操作。对该模型二维参数空间的系统探索还揭示了比原始一维版本更丰富的行为。此外,我们表明,纳入特定类型的轴突-轴突相互作用可以解释最近在一部分视网膜神经节细胞中对特定受体水平进行基因操作时观察到的图谱塌陷。这些结果共同表明,平衡对图谱发育的多种影响似乎是解释视网膜拓扑图谱形成中许多生物学现象的必要条件,并对潜在的生物学变量提出了重要限制。