MiR-29 coordinates age-dependent plasticity brakes in the adult visual cortex

Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular "brakes" limiting excessive rewiring beyond a critical period. The mechanisms coordinating the expression of these factors during the transition from development to adulthood remain unknown. We found that miR-29a expression in the visual cortex dramatically increases with age, but it is not experience-dependent. Precocious high levels of miR-29a blocked ocular dominance plasticity and caused an early appearance of perineuronal nets. Conversely, inhibition of miR-29a in adult mice using LNA antagomirs activated ocular dominance plasticity, reduced perineuronal nets and restored their juvenile chemical composition. Activated adult plasticity had the typical functional and proteomic signature of critical period plasticity. Transcriptomic and proteomic studies indicated that miR-29a manipulation regulates the expression of plasticity brakes mainly affecting parvalbumin-positive interneurons. These data indicate that miR29a is a master regulator of the plasticity brakes promoting age-dependent stabilization of visual cortical circuits. RNA-seq was performed on the visual cortex of adult mice intracortical injected with 1) LNA oligonucleotide with scrambled sequence (control), number of replicates = 4; or 2) intracortical injected with LNA oligonucleotide complementary to miR-29a (miR-29a), treated samples, number of replicates = 4.