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Mol Neurobiol. 2019 Aug;56(8):5701-5714. doi: 10.1007/s12035-019-1492-7. Epub 2019 Jan 23.

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

Author information

1
Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132, Genoa, Italy. anna.rocchi@iit.it.
2
IRCSS Ospedale Policlinico San Martino, 16132, Genoa, Italy. anna.rocchi@iit.it.
3
Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132, Genoa, Italy.
4
Department of Experimental Medicine, Section of Physiology, University of Genoa, Viale Benedetto XV 3, 16132, Genoa, Italy.
5
Institute of Neurology, Department of Clinical and Experimental Epilepsy, University College London, London, WC1N 3BG, UK.
6
IRCSS Ospedale Policlinico San Martino, 16132, Genoa, Italy.
7
Consiglio Nazionale delle Ricerche, Institute of Biophysics, Via De Marini 6, 16149, Genoa, Italy.

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.

KEYWORDS:

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

PMID:
30671783
DOI:
10.1007/s12035-019-1492-7

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