miR-26a and miR-384-5p are required for LTP maintenance and spine enlargement

Qin-Hua Gu, Danni Yu, Zhonghua Hu, Xing Liu, Yanqin Yang, Yan Luo, Jun Zhu () and Zheng Li ()
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Qin-Hua Gu: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health
Danni Yu: Purdue University
Zhonghua Hu: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health
Xing Liu: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health
Yanqin Yang: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health
Yan Luo: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health
Jun Zhu: Systems 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

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. It is associated with the formation and enlargement of dendritic spines—tiny protrusions accommodating excitatory synapses. Both LTP and spine remodelling are crucial for brain development, cognition and the pathophysiology of neurological disorders. The role of microRNAs (miRNAs) in the maintenance of LTP, however, is not well understood. Using next-generation sequencing to profile miRNA transcriptomes, we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3. Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities. This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate ‘LTP miRNAs’.

Date: 2015
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DOI: 10.1038/ncomms7789

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