Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, United Kingdom
Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA, United Kingdom.
eNeuro. 2023 Nov 21;10(11). doi: 10.1523/ENEURO.0135-23.2023. Print 2023 Nov.
It has been suggested that stochasticity acts in the formation of topographically ordered maps in the visual system through the opposing chemoaffinity and neural activity forces acting on the innervating nerve fibers being held in an unstable equilibrium. Evidence comes from the Islet2-EphA3 knock-in mouse, in which ∼50% of the retinal ganglion cells, distributed across the retina, acquire the EphA3 receptor, thus having an enhanced density of EphA which specifies retinotopic order along the rostrocaudal (RC) axis of the colliculus. Sampling EphA3 knock-in maps in heterozygotes at different positions along the mediolateral (ML) extent of the colliculus had found single 1D maps [as in wild types (WTs)], double maps (as in homozygous knock-ins) or both single and double maps. We constructed full 2D maps from the same mouse dataset. We found either single maps or maps where the visual field projects rostrally, with a part-projection more caudally to form a double map, the extent and location of this duplication varying considerably. Contrary to previous analyses, there was no strict demarcation between heterozygous and homozygous maps. These maps were replicated in a computational model where, as the level of EphA3 was increased, there was a smooth transition from single to double maps. Our results suggest that the diversity in these retinotopic maps has its origin in a variability over the retina in the effective amount of EphA3, such as through variability in gene expression or the proportion of EphA3+ retinal ganglion cells, rather than the result of competing mechanisms acting at the colliculus.
有人认为，通过作用于支配神经纤维的趋化性和神经活性力之间的拮抗作用，随机性在视觉系统中形成了具有地形排列的图谱。这种观点的证据来自于 Islet2-EphA3 基因敲入鼠，在这种鼠中，约 50%的视网膜神经节细胞（分布于整个视网膜）获得了 EphA3 受体，因此 EphA 的密度增加，沿视丘（colliculus）的前后轴（rostrocaudal，RC）特异性地排列视网膜神经节细胞。在视丘的中侧（mediolateral，ML）轴的不同位置，对 EphA3 基因敲入杂合子的图谱进行取样，发现了单个 1D 图谱（与野生型相同）、双个图谱（与纯合子基因敲入相同）或两者兼有。我们根据同一批鼠的数据构建了完整的 2D 图谱。我们发现，要么是单个图谱，要么是视场向前投射的图谱，一部分向后投射形成双个图谱，这种重复的程度和位置变化很大。与之前的分析相反，杂合子和纯合子图谱之间没有严格的界限。在计算模型中，这些图谱得到了复制，随着 EphA3 水平的增加，从单个图谱到双个图谱的转变是平滑的。我们的结果表明，这些视网膜拓扑图的多样性起源于 EphA3 在视网膜上的有效量的变化，这种变化可能是通过基因表达或 EphA3+视网膜神经节细胞的比例的变化引起的，而不是由于视丘上的竞争机制的作用。
