Hu Zhonghua, Yu Danni, Gu Qin-hua, Yang Yanqin, Tu Kang, Zhu Jun, Li Zheng
Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Department of Statistics, Purdue University, West Lafayette, Indiana 47907, USA.
Nat Commun. 2014;5:3263. doi: 10.1038/ncomms4263.
Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.
树突棘是大脑中容纳突触后特化结构的亚细胞区室，其活性依赖的修饰是大脑发育、认知以及脑部疾病突触病理学的重要细胞机制。N-甲基-D-天冬氨酸受体依赖的长时程抑制（NMDAR-LTD）是一种典型的突触可塑性形式，伴有树突棘的长期重塑。然而，NMDAR-LTD中持久树突棘重塑的潜在机制在很大程度上尚不清楚。在此，我们表明长时程抑制的诱导会导致影响许多细胞活动的微小RNA转录组发生全局性变化。具体而言，我们发现miR-191和miR-135的表达变化是维持而非诱导树突棘重构所必需的。此外，我们发现微小RNA会在较长时间内调节肌动蛋白解聚和AMPA受体胞吐作用，以支持持久的树突棘可塑性。这些发现揭示了一种微小RNA介导的机制以及AMPA受体胞吐作用在持久树突棘可塑性中的作用，并确定了一些参与长时程抑制的候选微小RNA。
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