MICRORNA-9 REGULATES DENDRITIC ARBORIZATION, SYNAPTIC NEUROTRANSMISSION AND SENSORIMOTOR RESPONSE

GIUSTI, SEBASTIÁN A.; REFOJO, DAMIÁN

Barga

Conferencia; RNA localisation and local translation; 2017

EMBO

MicroRNAs (miRNAs) are conserved noncoding RNAs that function as posttranscriptional regulators of gene expression. MiR-9 is one of the most abundant miRNAs in the brain. Although the function of miR-9 has been well characterised in neural progenitors, its role in dendritic and synaptic development remains largely unknown. In order to target miR-9 in vivo, we developed a transgenic miRNA sponge mouse line allowing conditional inactivation of the miR-9 family in a spatio-temporal-controlled manner. Using this novel approach, we found that miR-9 controls dendritic growth and synaptic transmission in vivo. Furthermore, we demonstrate that miR-9-mediated down-regulation of the transcriptional repressor REST is essential for proper dendritic growth. We performed an extensive behavioural phenotyping showing that depletion of miR-9 in the CNS did not affect cognitive, social or anxiety-related behaviors but led to an impairment in the mechanisms of sensorimotor response plasticity. Since some astrocytic markers are upregulated in miR-9 sponge expressing mice, a potential contribution of astrocytes to the behavioural phenotype was investigated. This study shows for the first time a mouse genetic tool that enables the inactivation of microRNAs in a temporospatial-controlled manner evidencing a crucial role of miR-9 in neuronal development and sensorimotor gating.