Meyer R L, Kageyama G H
Department of Developmental and Cell Biology, University of California, Irvine 92717, USA.
J Comp Neurol. 1999 Jun 28;409(2):299-312.
During the formation of visual maps, growing axons initially form a map by using topographically distributed cues that direct their growth and branching to the appropriate target region. This initial map is typically roughly retinotopic and is subsequently refined through activity-dependent rearrangement or cell death. Although synaptic connections are thought to be rearranged during the later refinement phase, there is no clear evidence that synapses are being formed during the initial targeting phase of development. Also, because optic fiber growth can be accurately directed during normal development, it is unclear whether regenerative fibers that have more pathway disorder would behave similarly. This issue was addressed by using optic fibers of goldfish that have the capacity to regenerate a retinotopic projection and can reestablish a rough retinotopic order without impulse activity. The optic nerve of goldfish was crushed, and at various times later, a small number of optic fibers in ventronasal retina was labeled with wheatgerm agglutinin-horseradish peroxidase. The tectum was then processed for electron microscopy to look at the distribution of labeled synapses during regeneration. At 3 weeks, synapses were observed at the far anterior end of the tectum and none were yet seen at the correct posterior retinotopic position. At 4-5 weeks, synapses were seen in nearly equal numbers at the incorrect anterior end and at both correct (retinotopic) and incorrect posterior positions. At late stages of regeneration, synapses were restricted to their correct posterior retinotopic position in the tectum, as they were in normal fish. These findings show that the formation of global retinotopic order entails the formation and subsequent elimination of a large number of highly ectopic synapses. Synaptic rearrangement is a major feature of targeting in this system and may be required for the regeneration of a retinotopic projection.
在视觉图谱形成过程中，生长中的轴突最初通过利用拓扑分布的线索来形成图谱，这些线索引导它们的生长和分支到达适当的目标区域。这个初始图谱通常大致是视网膜拓扑的，随后通过依赖活动的重排或细胞死亡进行细化。虽然人们认为突触连接在后期细化阶段会发生重排，但没有明确证据表明在发育的初始靶向阶段会形成突触。此外，由于在正常发育过程中视神经纤维的生长可以被精确引导，尚不清楚具有更多通路紊乱的再生纤维是否会有类似表现。通过使用具有再生视网膜拓扑投射能力且能在无冲动活动情况下重新建立大致视网膜拓扑顺序的金鱼视神经纤维来解决这个问题。将金鱼的视神经切断，在之后的不同时间，用小麦胚凝集素 - 辣根过氧化物酶标记腹鼻侧视网膜中的少量视神经纤维。然后对顶盖进行电子显微镜处理，以观察再生过程中标记突触的分布。在3周时，在顶盖的最前端观察到突触，而在正确的视网膜拓扑位置的后端尚未观察到突触。在4 - 5周时，在不正确的前端以及正确（视网膜拓扑）和不正确的后端位置观察到的突触数量几乎相等。在再生后期，突触如在正常鱼类中一样，局限于顶盖中正确的视网膜拓扑后端位置。这些发现表明，全局视网膜拓扑顺序的形成需要形成并随后消除大量高度异位的突触。突触重排是该系统靶向的一个主要特征，可能是视网膜拓扑投射再生所必需的。
