Co-option of CENP-A for activity-induced neuronal plasticity

We report that CENP-A plays a pivotal role in neuronal activation and subsequent memory formation in rodent hippocampus. More specifically, we find that CENP-A containing chromatin controls expression of Immediate Early Genes (IEGs); a set of transcriptional factors crucial for neuronal firing, long-term potentiation and memory formation. Downregulation of CENP-A impairs IEGs expression and causes memory defects. Furthermore, we show that this behavior of CENP-A is evolutionary conserved between rodents and humans, whereby human forebrain organoids display a similar dependency on CENP-A expression for neuronal activation. Therefore, we attribute a novel, mitotic-independent role to CENP-A in hippocampal neurons, thus providing direct evidence that a distinct chromatin state is a necessary requirement for memory formation. CENP-A Chip seq on dissected hippocampi from C57BL/6 mice. Paired experiement includes 4 mice per condition, total of 3 replicate experiments. Each experiment contains control group (Untreated) and PTZ-treated group.