MicroRNAs (miRNAs) are small non-coding RNAs conserved throughout evolution that are predicted to regulate more than half of protein coding genes. Although they have been shown to be important for neuronal development, differentiation and connectivity, very little is known about their role in experience-dependent cortical plasticity. We utilized visual deprivation paradigms to elucidate the role of miRNAs in visual cortex plasticity. Through a sequential analysis of miRNA expression with miRNA microarray, mature and pri-miRNA qRT-PCR we identified a subset of abundant miRNAs whose expression in mouse primary visual cortex was altered following dark-rearing (DR) and/or monocular deprivation (MD). Focusing on the most robustly affected miRNA in both DR and MD, miR-132, we further determined that its expression was distinctively increased during the critical period of visual cortex plasticity, and gradually normalized after light exposure following DR. Locked Nucleic Acid (LNA) in situ hybridization revealed that miR-132 reduction after DR and MD was specific to cortical layers 2/3 and 4. Neuronal inhibition of miR-132 availability in vivo, using the technology of miRNA “sponging”, resulted in a dose-dependent loss of ocular dominance plasticity in individual identified superficial layer neurons following short term MD. Notably, changes in dendritic spine density of miR-132 sponge infected neurons accompanied the observed functional deficits, and were in accordance with increased levels of miR-132 target p250GAP, a known inhibitor of spine growth. These data support a critical role for miR-132 in activity-dependent regulation of neuronal structure and function.

Society for Neuroscience Abstract, 2011.