Department of Molecular, Cell, and Developmental Biology, Santa Cruz Institute of Particle Physics, University of California, Santa Cruz, CA 95064, USA.
Proc Natl Acad Sci U S A. 2011 Nov 22;108(47):19060-5. doi: 10.1073/pnas.1102834108. Epub 2011 Nov 7.
Topographic maps are the primary means of relaying spatial information in the brain. Understanding the mechanisms by which they form has been a goal of experimental and theoretical neuroscientists for decades. The projection of the retina to the superior colliculus (SC)/tectum has been an important model used to show that graded molecular cues and patterned retinal activity are required for topographic map formation. Additionally, interaxon competition has been suggested to play a role in topographic map formation; however, this view has been recently challenged. Here we present experimental and computational evidence demonstrating that interaxon competition for target space is necessary to establish topography. To test this hypothesis experimentally, we determined the nature of the retinocollicular projection in Math5 (Atoh7) mutant mice, which have severely reduced numbers of retinal ganglion cell inputs into the SC. We find that in these mice, retinal axons project to the anteromedialj portion of the SC where repulsion from ephrin-A ligands is minimized and where their attraction to the midline is maximized. This observation is consistent with the chemoaffinity model that relies on axon-axon competition as a mapping mechanism. We conclude that chemical labels plus neural activity cannot alone specify the retinocollicular projection; instead axon-axon competition is necessary to create a map. Finally, we present a mathematical model for topographic mapping that incorporates molecular labels, neural activity, and axon competition.
地形图是大脑中传递空间信息的主要手段。几十年来，实验和理论神经科学家一直致力于研究它们形成的机制。视网膜向顶盖（SC）/顶盖的投射一直是一个重要的模型，用于表明渐变的分子线索和模式化的视网膜活动是地形图形成所必需的。此外，已经有人提出轴突间竞争在地形图形成中起作用；然而，这种观点最近受到了挑战。在这里，我们提出了实验和计算证据，证明轴突间对目标空间的竞争对于建立地形是必要的。为了在实验上验证这一假设，我们确定了 Math5（Atoh7）突变小鼠中的视网膜-顶盖投射的性质，该小鼠的视网膜神经节细胞输入 SC 的数量严重减少。我们发现，在这些小鼠中，视网膜轴突投射到 SC 的前内侧部分，这里来自 Ephrin-A 配体的排斥最小化，而它们对中线的吸引力最大化。这一观察结果与依赖轴突-轴突竞争作为映射机制的化学亲和性模型一致。我们得出结论，化学标签加神经活动本身不能指定视网膜-顶盖投射；相反，轴突-轴突竞争对于创建地图是必要的。最后，我们提出了一个包含分子标签、神经活动和轴突竞争的地形映射数学模型。
