The observed long-term memory impairments were associated with specific hippocampal long-term potentiation deficits and altered dendritic spine morphology. In general, BAF53b appears to be necessary for LTP consolidation as induction and initial expression of potentiation are normal. However, we did observe significantly increased initial potentiation in the high expressing transgenic line, which then showed a failure to stabilize similar to the low expressing line and the heterozygous knockout line. Interestingly, the more severe LTP phenotype in the BAF53bΔHDhigh mice compared to the BAF53ΔHDlow and Baf53b+/− het mice suggests that higher transgene expression alters the degree to which BAF53b effects induction, initial expression, and consolidation of LTP. Given recent findings that mutations in subunits of the mammalian BAF complex are linked with sporadic autism, sporadic mental retardation and syndromic intellectual disability12-16, the spectrum of synaptic plasticity and memory impairments found with our different manipulations of BAF53b could serve as a novel model for disorders such as Coffin-Siris and Nicolaides-Baraitser syndrome12-14, and intellectual disability in general.
