Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States.
Department of Neuroscience, Washington University School of Medicine, Saint Louis, United States.
Elife. 2018 Mar 19;7:e30388. doi: 10.7554/eLife.30388.
Synaptic cell adhesion molecules (CAMs) promote synapse formation in the developing nervous system. To what extent they maintain and can restore connections in the mature nervous system is unknown. Furthermore, how synaptic CAMs affect the growth of synapse-bearing neurites is unclear. Here, we use adeno-associated viruses (AAVs) to delete, re-, and overexpress the synaptic CAM NGL2 in individual retinal horizontal cells. When we removed NGL2 from horizontal cells, their axons overgrew and formed fewer synapses, irrespective of whether was deleted during development or in mature circuits. When we re-expressed NGL2 in knockout mice, horizontal cell axon territories and synapse numbers were restored, even if AAVs were injected after phenotypes had developed. Finally, overexpression of NGL2 in wild-type horizontal cells elevated synapse numbers above normal levels. Thus, NGL2 promotes the formation, maintenance, and restoration of synapses in the developing and mature retina, and restricts axon growth throughout life.
突触细胞粘附分子 (CAMs) 促进发育中神经系统的突触形成。它们在多大程度上维持和恢复成熟神经系统中的连接尚不清楚。此外，突触 CAM 如何影响带有突触的神经突的生长尚不清楚。在这里，我们使用腺相关病毒 (AAV) 在单个视网膜水平细胞中删除、重新表达和过表达突触 CAM NGL2。当我们从水平细胞中去除 NGL2 时，它们的轴突过度生长并形成更少的突触，无论在发育过程中还是在成熟回路中是否删除了 。当我们在敲除小鼠中重新表达 NGL2 时，水平细胞轴突区域和突触数量得到恢复，即使在表型出现后再注射 AAV。最后，在野生型水平细胞中过表达 NGL2 将突触数量提高到正常水平以上。因此，NGL2 促进了发育中和成熟的视网膜中突触的形成、维持和恢复，并限制了整个生命周期中轴突的生长。
