Parvalbumin cell ribosome profiling in adult enhanced plasticity paradigms reveals distinct molecular signatures compared to juvenile critical period plasticity

Abstract

The juvenile brain is shaped by critical periods (CPs) of plasticity regulated in part by parvalbumin (PV) interneurons. The "reopening" of CPs has been explored in brain disorders, yet it remains unclear whether adult enhanced plasticity recapitulates developmental mechanisms. We profiled visual cortex PV-specific ribosome-associated mRNAs at the CP peak and in two adult plasticity paradigms, chondroitinase ABC (ChABC) injection and extracellular OTX2 blockade. No shared translatomic signature emerged between the three conditions. Nonetheless, CP and ChABC-induced plasticity shared genes coding for synaptic components and extracellular matrix. Condition-specific pathways highlighted mechano-transduction and cytoskeletal remodeling for ChABC plasticity and DNA repair and heterochromatin for CP plasticity. These juvenile pathways were supported by elevated {gamma}H2AX, H3K9me3, and DAPI foci in PV cells uniquely during the CP. Thus, adult plasticity does not simply reinstate juvenile mechanisms, but instead may recruit partially overlapping, condition-specific molecular pathways revealing candidate targets for enhancing adult plasticity.