title: miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression.
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.
authors.affiliation: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Statistics, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Danni
authors.initials: D
authors.lastname: Yu
authors.affiliation: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Qin-hua
authors.initials: QH
authors.lastname: Gu
authors.affiliation: Genetics and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Genetics and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Tu
authors.affiliation: Genetics and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000502:physiology*; D005089:Exocytosis; D006624:Hippocampus / Q000378:metabolism*; D036881:Long-Term Synaptic Depression; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D016202:N-Methylaspartate; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D059467:Transcriptome; D051348:Tropomodulin / Q000378:metabolism
chemical_list: D000199:Actins; D033942:Adaptor Proteins, Vesicular Transport; C555937:MIRN191 microRNA, mouse; D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C495835:Tmod2 protein, rat; D051348:Tropomodulin; C095992:complexin I; C095993:complexin II; D016202:N-Methylaspartate