The noncoding circular RNA <i>circHomer1</i> regulates synaptic development and experience-dependent plasticity in the mouse visual cortex

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 <i>in vitro</i>, circRNA regulation by and function in experience-dependent plasticity <i>in vivo</i> 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 <i>Homer1</i> gene, <i>circHomer1</i> and <i>Homer1a,</i> respectively, showed opposing changes in expression following 3-day MD: <i>circHomer1</i> increased while <i>Homer1a</i> decreased. Knockdown of <i>circHomer1</i> delayed the depression of closed-eye responses normally observed after 3-day MD. <i>circHomer1</i>-knockdown reduced average dendritic spine size prior to MD but also blocked further MD-induced shrinkage, consistent with impaired structural plasticity. <i>circHomer1</i>-knockdown also prevented the reduction of surface AMPA receptors normally observed after 3-day MD. Our findings highlight the essential role of <i>circHomer1</i> in V1 synaptic development and experience-dependent plasticity.