MicroRNA-186-5p controls GluA2 surface expression and synaptic scaling in hippocampal neurons

Proceedings of the National Academy of Sciences of the United States of America
Mariline M SilvaAna Luísa Carvalho

Abstract

Homeostatic synaptic scaling is a negative feedback response to fluctuations in synaptic strength induced by developmental or learning-related processes, which maintains neuronal activity stable. Although several components of the synaptic scaling apparatus have been characterized, the intrinsic regulatory mechanisms promoting scaling remain largely unknown. MicroRNAs may contribute to posttranscriptional control of mRNAs implicated in different stages of synaptic scaling, but their role in these mechanisms is still undervalued. Here, we report that chronic blockade of glutamate receptors of the AMPA and NMDA types in hippocampal neurons in culture induces changes in the neuronal mRNA and miRNA transcriptomes, leading to synaptic upscaling. Specifically, we show that synaptic activity blockade persistently down-regulates miR-186-5p. Moreover, we describe a conserved miR-186-5p-binding site within the 3'UTR of the mRNA encoding the AMPA receptor GluA2 subunit, and demonstrate that GluA2 is a direct target of miR-186-5p. Overexpression of miR-186 decreased GluA2 surface levels, increased synaptic expression of GluA2-lacking AMPA receptors, and blocked synaptic scaling, whereas inhibition of miR-186-5p increased GluA2 surface leve...Continue Reading

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Citations

May 29, 2020·Genes & Genomics·Minseok Song
Dec 24, 2019·Frontiers in Cellular Neuroscience·Sandra DubesMathieu Letellier
Aug 23, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Subodh Kumar, P Hemachandra Reddy
Jan 14, 2021·Cells·Dolores Siedlecki-WullichJosé Rodríguez-Álvarez
Jul 19, 2021·Neuropharmacology·Jonathan G Hanley

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