Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Biozentrum, Life Sciences Training Facility, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland.
Cell. 2014 Mar 13;156(6):1153-1166. doi: 10.1016/j.cell.2014.01.054.
A plastic nervous system requires the ability not only to acquire and store but also to forget. Here, we report that musashi (msi-1) is necessary for time-dependent memory loss in C. elegans. Tissue-specific rescue demonstrates that MSI-1 function is necessary in the AVA interneuron. Using RNA-binding protein immunoprecipitation (IP), we found that MSI-1 binds to mRNAs of three subunits of the Arp2/3 actin branching regulator complex in vivo and downregulates ARX-1, ARX-2, and ARX-3 translation upon associative learning. The role of msi-1 in forgetting is also reflected by the persistence of learning-induced GLR-1 synaptic size increase in msi-1 mutants. We demonstrate that memory length is regulated cooperatively through the activation of adducin (add-1) and by the inhibitory effect of msi-1. Thus, a GLR-1/MSI-1/Arp2/3 pathway induces forgetting and represents a novel mechanism of memory decay by linking translational control to the structure of the actin cytoskeleton in neurons.
一个可塑性的神经系统不仅需要具备获取和存储的能力，还需要具备遗忘的能力。在这里，我们报告说，秀丽隐杆线虫中的 musashi (msi-1) 对于依赖时间的记忆丧失是必需的。组织特异性挽救表明，MSI-1 功能在 AVA 中间神经元中是必需的。通过 RNA 结合蛋白免疫沉淀 (IP)，我们发现 MSI-1 在体内与 Arp2/3 肌动蛋白分支调节复合物的三个亚基的 mRNA 结合，并在联想学习时下调 ARX-1、ARX-2 和 ARX-3 的翻译。msi-1 在遗忘中的作用也反映在 msi-1 突变体中学习诱导的 GLR-1 突触大小增加的持续存在上。我们证明，记忆长度通过 adducin (add-1) 的激活和 msi-1 的抑制作用来协同调节。因此，GLR-1/MSI-1/Arp2/3 途径诱导遗忘，并通过将翻译控制与神经元中肌动蛋白细胞骨架的结构联系起来，代表了一种记忆衰减的新机制。
