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

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  • Zhonghua Hu

    (Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health)

  • Danni Yu

    (Purdue University, West Lafayette, Indiana)

  • Qin-hua Gu

    (Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health)

  • Yanqin Yang

    (Genetics and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health)

  • Kang Tu

    (Genetics and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health)

  • Jun Zhu

    (Genetics and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health)

  • Zheng Li

    (Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health)

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.

Suggested Citation

  • Zhonghua Hu & Danni Yu & Qin-hua Gu & Yanqin Yang & Kang Tu & Jun Zhu & Zheng Li, 2014. "miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression," Nature Communications, Nature, vol. 5(1), pages 1-17, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4263
    DOI: 10.1038/ncomms4263
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