Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
Buck Institute for Research on Aging, Novato, CA 94945, USA.
Cell Rep. 2018 Apr 3;23(1):11-22. doi: 10.1016/j.celrep.2018.03.040.
Throughout the developing nervous system, considerable synaptic re-organization takes place as postsynaptic neurons extend dendrites and incoming axons refine their synapses, strengthening some and eliminating others. It is well accepted that these processes rely on synaptic activity; however, the mechanisms that lead to this developmental reorganization are not fully understood. Here, we explore the regulation of cap-dependent translation, a mechanism known to play a role in synaptic growth and plasticity. Using sympathetic ganglia in α3 nicotinic acetylcholine receptor (nAChR)-knockout (KO) mice, we establish that electrophysiologically silent synapses between preganglionic axons and postsynaptic sympathetic neurons do not refine, and the growth of dendrites and the targeting of synapses on postsynaptic neurons are impaired. Remarkably, genetically removing 4E-BP, a suppressor of cap-dependent translation, from these α3 nAChR-KO mice largely restores these features. We conclude that synaptic connections can re-organize and refine without postsynaptic activity during post-natal development when 4E-BP-regulated cap-dependent translation is enhanced.
在整个发育中的神经系统中，随着突触后神经元延伸树突和传入轴突细化其突触，一些突触得到加强，而另一些则被消除，会发生大量的突触重新组织。人们普遍认为这些过程依赖于突触活动；然而，导致这种发育性重新组织的机制尚未完全理解。在这里，我们探讨了帽依赖翻译的调节，这是一种已知在突触生长和可塑性中起作用的机制。使用α3 烟碱型乙酰胆碱受体 (nAChR) 敲除 (KO) 小鼠的交感神经节，我们确定了节前轴突和突触后交感神经元之间电生理上不活跃的突触不会细化，并且树突的生长和突触在突触后神经元上的靶向受到损害。值得注意的是，从这些α3 nAChR-KO 小鼠中基因去除 4E-BP（帽依赖翻译的抑制剂）在很大程度上恢复了这些特征。我们得出结论，当 4E-BP 调节的帽依赖翻译增强时，突触连接可以在出生后发育过程中无需突触后活动而重新组织和细化。
