Neurite-Enriched MicroRNA-218 Stimulates Translation of the GluA2 Subunit and Increases Excitatory Synaptic Strength

Anna Rocchi*, Daniela Moretti, Gabriele Lignani, Elisabetta Colombo, Joachim Scholz-Starke, Pietro Baldelli, Tatiana Tkatch, Fabio Benfenati

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Local control of protein translation is a fundamental process for the regulation of synaptic plasticity. It has been demonstrated that the local protein synthesis occurring in axons and dendrites can be shaped by numerous mechanisms, including miRNA-mediated regulation. However, several aspects underlying this regulatory process have not been elucidated yet. Here, we analyze the differential miRNA profile in cell bodies and neurites of primary hippocampal neurons and find an enrichment of the precursor and mature forms of miR-218 in the neuritic projections. We show that miR-218 abundance is regulated during hippocampal development and by chronic silencing or activation of neuronal network. Overexpression and knockdown of miR-218 demonstrated that miR-218 targets the mRNA encoding the GluA2 subunit of AMPA receptors and modulates its expression. At the functional level, miR-218 overexpression increases glutamatergic synaptic transmission at both single neuron and network levels. Our data demonstrate that miR-218 may play a key role in the regulation of AMPA-mediated excitatory transmission and in the homeostatic regulation of synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)5701-5714
Number of pages14
JournalMolecular Neurobiology
Volume56
Issue number8
DOIs
StatePublished - Aug 15 2019

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Keywords

  • GluA2
  • Homeostatic plasticity
  • Local translation
  • Neurite-specific microRNAs

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Rocchi, A., Moretti, D., Lignani, G., Colombo, E., Scholz-Starke, J., Baldelli, P., Tkatch, T., & Benfenati, F. (2019). Neurite-Enriched MicroRNA-218 Stimulates Translation of the GluA2 Subunit and Increases Excitatory Synaptic Strength. Molecular Neurobiology, 56(8), 5701-5714. https://doi.org/10.1007/s12035-019-1492-7