Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Nam-Gu, 37673 Pohang, Korea.
Department of Life Sciences, Pohang University of Science and Technology, Nam-Gu, 37673 Pohang, Korea.
Proc Natl Acad Sci U S A. 2019 May 7;116(19):9616-9621. doi: 10.1073/pnas.1819374116. Epub 2019 Apr 24.
Dendritic spines are major loci of excitatory inputs and undergo activity-dependent structural changes that contribute to synaptic plasticity and memory formation. Despite the existence of various classification types of spines, how they arise and which molecular components trigger their structural plasticity remain elusive. microRNAs (miRNAs) have emerged as critical regulators of synapse development and plasticity via their control of gene expression. Brain-specific miR-134s likely regulate the morphological maturation of spines, but their subcellular distributions and functional impacts have rarely been assessed. Here, we exploited atomic force microscopy to visualize in situ miR-134s, which indicated that they are mainly distributed at nearby dendritic shafts and necks of spines. The abundance of miR-134s varied between morphologically and functionally distinct spine types, and their amounts were inversely correlated with their postulated maturation stages. Moreover, spines exhibited reduced contents of miR-134s when selectively stimulated with beads containing brain-derived neurotropic factor (BDNF). Taken together, in situ visualizations of miRNAs provided unprecedented insights into the "inverse synaptic-tagging" roles of miR-134s that are selective to inactive/irrelevant synapses and potentially a molecular means for modifying synaptic connectivity via structural alteration.
树突棘是兴奋性输入的主要部位，经历活动依赖性的结构变化，这些变化有助于突触可塑性和记忆形成。尽管存在各种类型的棘突分类，但它们是如何产生的，以及哪些分子成分触发它们的结构可塑性仍然难以捉摸。microRNAs (miRNAs) 通过控制基因表达，已成为突触发育和可塑性的关键调节因子。脑特异性 miR-134s 可能调节棘突的形态成熟，但它们的亚细胞分布和功能影响很少被评估。在这里，我们利用原子力显微镜原位可视化 miR-134s，表明它们主要分布在棘突的附近树突干和颈部。miR-134s 的丰度在形态和功能上不同的棘突类型之间有所不同，其数量与它们假定的成熟阶段呈反比。此外，当用含有脑源性神经营养因子 (BDNF) 的珠子选择性刺激棘突时，miR-134s 的含量减少。总之，miRNAs 的原位可视化提供了前所未有的见解，即 miR-134s 具有“反向突触标记”作用，这种作用是针对不活跃/不相关的突触的，并且可能是通过结构改变来修饰突触连接的一种分子手段。
