Plasticity state-dependent changes in visual cortex parvalbumin interneuron mRNA translation and chromatin

The juvenile brain is shaped by critical periods of heightened plasticity whose timing is regulated by the maturation of parvalbumin interneurons. Gene expression during brain developmental is regulated by neuronal activity, which can trigger the formation of DNA double-strand breaks on early response genes regulatory elements. To determine if critical period plasticity induces double-strand breaks ({gamma}H2AX foci) and alters chromatin structure (DAPI foci) of parvalbumin cells, we analyzed the primary visual cortex of mice at peak ocular dominance plasticity (postnatal day P30) and in the non-plastic adult (at P90-P100). We also measured the expression of LINE-1 retrotransposons, known to induce double-strand breaks. Foci numbers and LINE-1 Orf1p expression were increased at P30 specifically in parvalbumin cells. TRAP-based RNA sequencing confirmed that LINE-1 translation in parvalbumin cells is activated at P30 compared to P100. ChABC injections in primary visual cortex were performed to determine whether reopened adult plasticity recapitulates the P30 translatome of parvalbumin cells. While the P30 TRAP was enriched for ion channel, postsynaptic membrane, and extracellular matrix components, the ChABC P100 TRAP was enriched for cytoskeletal structure and receptor binding proteins. Furthermore, ChABC treatment did not alter foci distribution or LINE-1 translation. These results suggest that juvenile critical periods promote genomic instability in parvalbumin cells and that adult plasticity reopened by ChABC is distinct from critical period plasticity.