Epigenetic mechanisms of gene regulation are emerging as a critical mechanism underlying long-term memory processes. The majority of the evidence supporting this idea comes from examination of chromatin modification (e.g. histone acetylation) and DNA methylation. However, nucleosome remodeling, which represents a third major epigenetic mechanism involved in regulating gene expression that has been shown to work together with chromatin modification and DNA methylation in yeast and cancer research, has yet to be investigated with regard to cognitive function. It has become increasingly important to understand the role of nucleosome remodeling considering the recent studies showing that mutations in the BAF complex are associated with intellectual disability disorders in humans12-14. In this study, we show that both a dominant negative and heterozygous knockout of BAF53b produces severe long-term memory and LTP consolidation impairments, providing the first evidence that nucleosome remodeling plays a critical role in synaptic plasticity and memory. The reintroduction of BAF53b into dorsal hippocampus using adeno-associated virus rescued long-term memory deficits in the Baf53b+/− het mice, providing clear evidence for the role of BAF53b in memory formation in the
