title: 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.
authors.affiliation: Institute of Cell Biology and Neurobiology, National Research Council, Via del Fosso di Fiorano, 64/65, 00143, Roma, Italy; Fondazione Santa Lucia Via del Fosso di Fiorano, 64/65, 00143, Roma, Italy.
authors.forename: Gisella
authors.initials: G
authors.lastname: Vetere
authors.forename: Christian
authors.initials: C
authors.lastname: Barbato
authors.forename: Silvia
authors.initials: S
authors.lastname: Pezzola
authors.forename: Paola
authors.initials: P
authors.lastname: Frisone
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aceti
authors.forename: MariaTeresa
authors.initials: M
authors.lastname: Ciotti
authors.forename: Carlo
authors.initials: C
authors.lastname: Cogoni
authors.forename: Martine
authors.initials: M
authors.lastname: Ammassari-Teule
authors.forename: Francesca
authors.initials: F
authors.lastname: Ruberti
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003214:Conditioning, Classical / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D064326:MEF2 Transcription Factors / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D064326:MEF2 Transcription Factors; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D027981:Symporters; D000096922:K Cl- Cotransporters; C525080:CPEB3 protein, rat; C477603:Cpeb3 protein, mouse; C578045:MEF2D protein, rat; C000592377:MIRN92 microRNA, rat; C578044:Mef2d protein, mouse; C541873:Mirn92 microRNA, mouse
keywords: contextual fear conditioning; dendritic spines; hippocampus; miR-92; microRNA