RESUMO
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.
Assuntos
Hipocampo/metabolismo , MicroRNAs/metabolismo , Plasticidade Neuronal/genética , Aprendizagem Espacial/fisiologia , Memória Espacial/fisiologia , Animais , Hipocampo/efeitos dos fármacos , Masculino , Memória de Longo Prazo/efeitos dos fármacos , Memória de Longo Prazo/fisiologia , Camundongos , MicroRNAs/genética , MicroRNAs/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Memória Espacial/efeitos dos fármacosRESUMO
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.
