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

ABSTRACT: Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular "brakes" limiting excessive circuit rewiring beyond a critical period. How the appearance of these factors is coordinated during the transition from development to adulthood remains unknown. We analyzed the role of miR-29a, a miRNA targeting factors involved in several important pathways for plasticity such as extracellular matrix and chromatin regulation. We found that visual cortical miR-29a expression in the visual cortex dramatically increases with age, but it is not experience-dependent. Precocious high levels of miR-29a induced by targeted intracortical injections of a miR-29a mimic 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 net intensity and number, and changed their chemical composition restoring permissive low chondroitin 4-O-sulfation levels characteristic of juvenile mice. Activated adult plasticity had the typical functional and proteomic signature of juvenile plasticity. Transcriptomic and proteomic studies indicated that miR-29a manipulation regulates the expression of plasticity factors acting at different cellular levels, from chromatin regulation to synaptic organization and extracellular matrix remodeling. Intriguingly, the projection of miR-29a regulated gene dataset onto cell-specific transcriptomes revealed that parvalbumin-positive interneurons and oligodendrocytes were the most affected cells. Overall, miR29a is a master regulator of the age-dependent plasticity brakes promoting stability of visual cortical circuits.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Erika Kelmer Sacramento  

LAB HEAD: Alessandro Cellerino

PROVIDER: PXD016430 | Pride | 2020-11-04

REPOSITORIES: Pride