Transcriptomics of critical period of visual cortical plasticity in mice

Abstract

In contrast to the prenatal development of the cerebral cortex, when cell production, migration, and layer formation dominate, development after birth involves more subtle processes, such as activity-dependent plasticity that includes refinement of synaptic connectivity by its stabilization and elimination. In the present study, we use RNA-seq with high spatial resolution to examine differential gene expression across layers 2/3, 4, 5, and 6 of the mouse visual cortex before the onset of the critical period of plasticity [postnatal day 5 (P5)], at its peak (P26), and at the mature stage (P180) and compare it with the prefrontal association area. We find that, although genes involved in early developmental events such as cell division, neuronal migration, and axon guidance are still prominent at P5, their expression largely terminates by P26, when synaptic plasticity and associated signaling pathways become enriched. Unexpectedly, the gene expression profile was similar in both areas at this age, suggesting that activity-dependent plasticity between visual and association cortices are subject to the same genetic constraints. Although gene expression changes follow similar paths until P26, we have identified 30 regionally enriched genes that are prominent during the critical period. At P180, we identified several hundred differentially expressed gene isoforms despite subsiding levels of gene expression differences. This result indicates that, once genetic developmental programs cease, the remaining morphogenetic processes may depend on posttranslational events.