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

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. © 2014 Wiley Periodicals, Inc.