Figure 4.

Smaller dendritic spines and thinner PSDs in Shank1 mutant mice. A, DiI-labeled dendrites from CA1 pyramidal neurons of adult wild-type (+/+) and Shank1^−/− mice (three representative segments shown). Scale bar, 5 μm. B, Quantification of dendritic spine density in wild-type versus Shank1^−/− neurons. Data are presented as scattergrams (with mean ± SEM superimposed), each point corresponds to the mean spine density for a single neuron (+/+, n = 33 neurons from 4 animals; −/−, n = 27 neurons from 4 animals). Shank1^−/− mice show a slight reduction in spine density (p < 0.05; t test). A total of 9210 wild-type spines and 7797 mutant spines were measured. C, D, Cumulative frequency plots for spine length (C) and spine head width (D) from wild-type (black line) and Shank1^−/− mice (gray line). Scattergrams, with mean ± SEM, are shown at the right. Shank1^−/− mice showed a small but highly significant shift toward smaller spines (length, p < 0.0005, K–S; width, p < 0.001, K–S). E, Representative electron micrographs of hippocampal CA1 striatum radiatum synapses from wild-type and Shank1^−/− mice. The PSD is visible as an electron-dense layer adjacent to the postsynaptic membrane. Note thinner PSD in Shank1^−/− synapses. Scale bar, 100 nm. F, G, Cumulative frequency distribution of PSD length (F) and thickness (G) from wild-type (black line) and Shank1^−/− mice (gray line). Sixty randomly selected synapses from each of four wild-type and six Shank1^−/− mice were measured by blind observers.