In view of the localization of the profound functional synaptic deficits to the post-synaptic compartment in BAF53ΔHDhigh mice (Fig 5), we assessed more closely the number and structure of dendritic spines, the sites of post-synaptic elements. Crossing the BAF53ΔHDhigh mice with a line expressing YFP under the Thy1 promoter in pyramidal cells, we confirmed the overall normal anatomy of the hippocampus (Supplemental Fig S5A). We then analyzed the spectrum of spine types (Supplemental Fig S5B) encompassing subpopulations of thin, stubby and mushroom-like spines25-27. The overall density of dendritic spines was modestly lower in BAF53bΔHDhigh mice compared with controls (Supplemental Fig S5F). However, a significant decrease in thin spines was apparent in the assessed CA1 pyramidal cells, including both main (stem) and oblique apical branches, resulting in an abnormally low ratio of thin / mushroom spines (Supplemental Fig S5C-E). The abnormal distribution of dendritic spine subpopulations already in juvenile BAF53bΔHDhigh mice is consistent with the problems in synaptic function and plasticity found in these mice. Together with data from Figure 6, these results indicate that BAF53b may have roles in both spine morphology/structure as well as synaptic events depending on the type of Baf53b mutation.
