FIG 8.
Brg1 is required for MEF2C-induced dendritic spine elimination. (A and B) Brg1 is required for MEF2C-mediated dendritic spine elimination in cultured hippocampal neurons. BAF53b-Cre Brg1F/F mutant and control hippocampal neuron cultures were transfected with plasmids expressing GFP and MEF2C, MEF2-VP16, or control MEF2Δ-VP16 at 7 DIV. GFP-labeled neurons were imaged at 14 DIV (A), and dendritic spine densities were measured and compared (B). (C to E) Organotypic hippocampal slice cultures from P6 Brg1F/F mice were biolistically transfected with plasmids for expression of Cre, GFP, and MEF2C or a control at 1 DIV. GFP-labeled CA1 neurons were imaged after 5 days (C), and the dendritic spine densities (D) and classifications (E) were analyzed. Scale bar, 5 μm. Values in the graphs are averages + standard errors. **, P < 0.01; *, P < 0.05 (analysis of variance with a post hoc t test). The numbers of neurons examined in each group are shown in the bar graph. (F) A model illustrating the function of Brg1 in synapse development and plasticity. During synaptic development, nBAF complexes are recruited by specific transcription factors to regulate expression of a significant number of genes required for synapse formation and maturation (left panel). In response to neuronal activity-triggered Ca2+ signaling, activated MEF2 proteins recruit nBAF complexes to MEF2 targets and regulate the activity-induced genes required for synapse elimination and plasticity (right panel). These two scenarios are not mutually exclusive and may reflect the different developmental stages of neurons.