Synaptic Activity Causes Minute-scale Changes in BAF Complex Composition and Function

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Deleterious mutations in SWI/SNF/BAF complexes are linked to intellectual disabilities and autism spectrum disorder.
• Synaptic activity regulates neuronal function, learning, and memory through rapid transcriptional changes.
• The immediate effects of neural activity on BAF complexes remain largely unknown.

Purpose of the Study:

• To investigate the minute-scale biochemical consequences of neural activity on BAF complexes.
• To define activity-dependent BAF complex alterations and their functional impact on transcription.

Main Methods:

• Primary cortical neurons from embryonic mice were subjected to membrane depolarization to model neural activity.
• Acute chemical perturbations assessed BAF ATPase activity and kinase signaling.
• Changes in BAF subunit composition, phosphorylation, and chromatin accessibility were analyzed.

Main Results:

• Within 10 minutes of depolarization, BAF complexes exhibited altered subunit composition and selective phosphorylation.
• Increased Baf200/Arid2 levels correlated with chromatin opening at specific DNA motifs.
• BAF modifications regulated chromatin accessibility for neurogenesis transcription factors, integrating upstream signaling pathways.

Conclusions:

• BAF complexes rapidly respond to neural activity by altering their composition and phosphorylation state.
• These dynamic BAF changes facilitate transcription factor binding and regulate gene expression crucial for neuronal function.
• The findings elucidate a membrane-to-nucleus signaling cascade involving BAF in activity-dependent gene regulation.