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Selective inhibition of miR-92 in hippocampal neurons alters contextual fear memory

Authors :
Vetere, G.
Barbato, C.
Pezzola, S.
Frisone, P.
Aceti, M.
Ciotti, M. T.
Cogoni, Carlo
Ammassari Teule, M.
Ruberti, F.
Source :
Hippocampus. 24(12)
Publication Year :
2014

Abstract

Post-transcriptional gene regulation mediated by microRNAs (miRNAs) is implicated in memory formation; however, the function of miR-92 in this regulation is uncharacterized. The present study shows that training mice in contextual fear conditioning produces a transient increase in miR-92 levels in the hippocampus and decreases several miR-92 gene targets, including: (i) the neuronal Cl(-) extruding K(+) Cl(-) co-transporter 2 (KCC2) protein; (ii) the cytoplasmic polyadenylation protein (CPEB3), an RNA-binding protein regulator of protein synthesis in neurons; and (iii) the transcription factor myocyte enhancer factor 2D (MEF2D), one of the MEF2 genes which negatively regulates memory-induced structural plasticity. Selective inhibition of endogenous miR-92 in CA1 hippocampal neurons, by a sponge lentiviral vector expressing multiple sequences imperfectly complementary to mature miR-92 under the control of the neuronal specific synapsin promoter, leads to up-regulation of KCC2, CPEB3 and MEF2D, impairs contextual fear conditioning, and prevents a memory-induced increase in the spine density. Taken together, the results indicate that neuronal-expressed miR-92 is an endogenous fine regulator of contextual fear memory in mice.

Details

ISSN :
10981063
Volume :
24
Issue :
12
Database :
OpenAIRE
Journal :
Hippocampus
Accession number :
edsair.pmid.dedup....9556d3d0bd4f80efd907d4a11407e094