RESUMEN
MicroRNAs are endogenous, noncoding RNAs crucial for the post-transcriptional regulation of gene expression. In this study, we investigated the role of miR-335-5p in spatial learning and synaptic plasticity. To this end we first showed spatial learning induced down-regulation of miR-335-5p. Next we found impairment in long-term memory and reduction in hippocampal long-term potentiation by exogenous administration of the miRNA. These findings demonstrate that miR-335-5p is a key coordinator of the intracellular pathways that mediate experience-dependent changes in the brain.
Asunto(s)
Hipocampo/metabolismo , MicroARNs/metabolismo , Plasticidad Neuronal/genética , Aprendizaje Espacial/fisiología , Memoria Espacial/fisiología , Animales , Hipocampo/efectos de los fármacos , Masculino , Memoria a Largo Plazo/efectos de los fármacos , Memoria a Largo Plazo/fisiología , Ratones , MicroARNs/genética , MicroARNs/farmacología , Plasticidad Neuronal/efectos de los fármacos , Aprendizaje Espacial/efectos de los fármacos , Memoria Espacial/efectos de los fármacosRESUMEN
MicroRNAs are endogenous, noncoding RNAs crucial for the post-transcriptional regulation of gene expression. Their role in spatial memory formation, however, is poorly explored. In this study, we analyzed learning-induced microRNA expression in the hippocampus and in the ventral striatum. Among miRNAs specifically downregulated by spatial training, we focused on the hippocampus-specific miR-324-5p and the ventral striatum-specific miR-24. In vivo overexpression of the two miRNAs demonstrated that miR-324-5p is able to impair memory if administered in the hippocampus but not in the ventral striatum, while the opposite is true for miR-24. Overall, these findings demonstrate a causal relationship between miRNA expression changes and spatial memory formation. Furthermore, they provide support for a regional dissociation in the post-transcriptional processes underlying spatial memory in the two brain structures analyzed.