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

Gisella Vetere, Christian Barbato, Silvia Pezzola, Paola Frisone, Massimiliano Aceti, Mariateresa Ciotti, Carlo Cogoni, Martine Ammassari-Teule, Francesca Ruberti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1458-1465
Number of pages8
JournalHippocampus
Volume24
Issue number12
DOIs
Publication statusPublished - Dec 1 2014

Keywords

  • Contextual fear conditioning
  • Dendritic spines
  • Hippocampus
  • MicroRNA
  • MiR-92

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Medicine(all)

Fingerprint Dive into the research topics of 'Selective inhibition of miR-92 in hippocampal neurons alters contextual fear memory'. Together they form a unique fingerprint.

Cite this