Synaptic activity causes minute-scale changes in BAF complex composition and function.

Genes encoding subunits of the BAF ATP-dependent chromatin remodeling complex are among the most enriched for deleterious de novo mutations in intellectual disabilities and autism spectrum disorder, but the causative molecular pathways are not understood. Synaptic activity in neurons is critical for learning, memory, and proper neural development. While BAF is required for activity-dependent developmental processes, such as dendritic outgrowth, the immediate molecular consequences of neuronal activity on BAF complexes are unknown. Here, we report that neuronal activity induces dramatic remodeling of the subunit composition of BAF complexes within 15 min, concurrent with both phosphorylation and dephosphorylation of its subunits. These biochemical effects are a convergent phenomenon downstream of multiple calcium-activated signaling pathways in mouse neurons and mouse fibroblasts and correspond to changes in BAF-dependent chromatin accessibility. Our studies imply that BAF decodes signals at the membrane by altering the combinatorial composition of its subunits.