Replacement of endogenous TrkC with exogenous TrkC WT, but not with TrkC mutants, rescues TrkC-mediated regulation of postsynapse density. A, Cultured hippocampal neurons were transfected with a lentiviral vector expressing sh-Control, sh-TrkC (TrkC KD) or coexpressing sh-TrkC and various TrkC constructs (WT and point mutants presented in Figs. 6 and 7) at DIV8 and analyzed at DIV14 by double immunofluorescence with antibodies to EGFP (green) and Shank1 (a postsynaptic marker; red). Scale bar, 10 μm (applies to all images). Note that the TrkC shRNA sequence used here targets 3′-UTRs of rat TrkC (see Fig. 8B). B, Summary graphs of the effects of TrkC molecular replacement in neurons on puncta density (left), puncta size (middle), and puncta intensity (right) measured using Shank1 as a synaptic marker. Two or three dendrites per transfected neuron were analyzed and group averaged. All data are shown as means ± SEM (*p < 0.05, ²*p < 0.01, ³*p < 0.001; ANOVA with post hoc Tukey's test). “n” denotes the number of neurons as follows: sh-Control/Shank1, n = 28; sh-TrkC/Shank1, n = 20; TrkC WT rescue/Shank1, n = 28; TrkC D240A/D242A rescue/Shank1, n = 23; TrkC N366A/T369A rescue/Shank1, n = 21; TrkC Y516F rescue/Shank1, n = 22; TrkC Y820F rescue/Shank1, n = 21; TrkC D679N rescue/Shank1, n = 21; and TrkC E543D rescue/Shank1, n = 25.