MiR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression

Zhonghua Hu, Danni Yu, Qin Hua Gu, Yanqin Yang, Kang Tu, Jun Zhu, Zheng Li

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

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.

Original languageEnglish
Article number3263
JournalNature Communications
Volume5
DOIs
StatePublished - 18 Feb 2014
Externally publishedYes

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