The noncoding circular RNA circHomer1 regulates synaptic development and experience-dependent plasticity in the mouse...

Circular RNAs (circRNAs) are closed-loop, single-stranded RNAs particularly enriched in the brain. Despite this enrichment, and evidence showing that synaptic development and plasticity alter their expression in vitro, circRNA regulation by and function in experience-dependent plasticity in vivo remain unexplored. Through transcriptome-wide analysis in juvenile mouse primary visual cortex (V1) following monocular deprivation (MD), we identified that the circular and the activity-dependent mRNA forms of the Homer1 gene, circHomer1 and Homer1a, respectively, showed opposing changes in expression following 3-day MD: circHomer1 increased while Homer1a decreased. Knockdown of circHomer1 delayed the depression of closed-eye responses normally observed after 3-day MD. circHomer1-knockdown reduced average dendritic spine size prior to MD but also blocked further MD-induced shrinkage, consistent with impaired structural plasticity. circHomer1-knockdown also prevented the reduction of surface AMPA receptors normally observed after 3-day MD. Our findings highlight the essential role of circHomer1 in V1 synaptic development and experience-dependent plasticity.