TY - JOUR
T1 - Selective inhibition of miR-92 in hippocampal neurons alters contextual fear memory
AU - Vetere, Gisella
AU - Barbato, Christian
AU - Pezzola, Silvia
AU - Frisone, Paola
AU - Aceti, Massimiliano
AU - Ciotti, Mariateresa
AU - Cogoni, Carlo
AU - Ammassari-Teule, Martine
AU - Ruberti, Francesca
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
KW - Contextual fear conditioning
KW - Dendritic spines
KW - Hippocampus
KW - MicroRNA
KW - MiR-92
UR - http://www.scopus.com/inward/record.url?scp=84910153513&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84910153513&partnerID=8YFLogxK
U2 - 10.1002/hipo.22326
DO - 10.1002/hipo.22326
M3 - Article
C2 - 24990518
AN - SCOPUS:84910153513
VL - 24
SP - 1458
EP - 1465
JO - Hippocampus
JF - Hippocampus
SN - 1050-9631
IS - 12
ER -