Differential contributions of Shank3 isoforms to excitatory synapses. (A) Co-localization of Shank3 isoforms with PSD-95. Shank3 isoforms tagged with GFP (green) were expressed in primary hippocampal neurons and co-stained with an excitatory post-synaptic marker PSD-95 (red). Shank3 isoforms displayed differential impacts on the size (B) and density (C) of PSD-95 puncta. (D) Impacts of Shank3 isoforms on dendritic spine morphology. EGFP-Shank3 isoforms (green) were co-transfected with tdTomato (red) in hippocampal neurons. Shank3 isoforms displayed differential effects on spine density (E) and spine length (F) of hippocampal neurons. All data are shown as mean ± SEM. *, P <0.01, compared to GFP; #, P <0.01, compared to Shank3a, two tail t-test. Scale bar: 10 μm.