eAβos reduce NMDA sEPSC amplitude in cortical slice neurons from WT but not from APP KO mice. A, Representative traces of NMDA sEPSCs recorded in WT neurons from Swiss mice at T₀ and T₂₀ in control condition; with eAβos. B, Bar graphs (mean ± SEM) showing the T₂₀/T₀ ratio of NMDA sEPSC amplitude and frequency recorded in WT neurons from Swiss mice in control condition (white bars; n = 11 neurons, N = 9 mice, Wilcoxon W = 22(44, −22), p = 0.3652, for sEPSC amplitudes; and Wilcoxon W = −16(25, −41), p = 0.5195, for sEPSC frequencies); with eAβos (gray bars; n = 16 neurons, N = 8 mice, Wilcoxon W = −114(11, −125), p = 0.0017, for sEPSC amplitudes; and Wilcoxon W = −84(26, −110), p = 0.0290 for sEPSC frequencies); with eAβ monomers [eAβ(mo), 300 nm; light gray bars; n = 8 neurons, N = 4 mice, Wilcoxon W = 6(21, −15), p = 0.7422, for sEPSC amplitudes; and Wilcoxon W = 8(22, −14), p = 0.6406, for sEPSC frequencies). One-way ANOVA and Tukey's post hoc test for multiple comparisons (F_(2,32) = 5.578, p = 0.0084; control vs eAβos; p = 0.0423, eAβos vs eAβ(mo), p = 0.0143] for NMDA sEPSC amplitudes and Kruskal–Wallis followed by Dunn's multiple-comparisons test (5.076, p = 0.0790, for NMDA sEPSC frequencies. C, Representative traces of NMDA sEPSCs recorded in APP KO neurons at T₀ and T₂₀ in control condition, with eAβos. D, Bar graphs (mean ± SEM) showing the T₂₀/T₀ ratio of NMDA sEPSC amplitude and frequency recorded in APP KO neurons in control condition (white bars; n = 6 neurons, N = 6 mice, Wilcoxon W = 1(11, −10), p > 0.9999, for sEPSC amplitudes; and Wilcoxon W = −3(9, −12), p = 0.8438, for sEPSC frequencies); in WT neurons from C57BL/6J mice with eAβos (gray bars; n = 6 neurons, N = 3 mice, Wilcoxon W = −21(0, −21), p = 0.0313, for sEPSC amplitudes; and Wilcoxon W = −21(0, −21), p = 0.0313, for sEPSC frequencies); in APP KO neurons with eAβos (light gray bars; n = 8 neurons, N = 5 mice, Wilcoxon W = 18(27, −9), p = 0.2500, for sEPSC amplitudes; and Wilcoxon W = −36(0, −36), p = 0.0078, for sEPSC frequencies). One-way ANOVA and Tukey's post hoc test for multiple comparisons [F_(2,17) = 6.792; p = 0.0068; control(APP KO) vs eAβos p = 0.0298; eAβos vs eAβos (APP KO), p = 0.0072] for NMDA sEPSC amplitudes, and one-way ANOVA followed by Tukey's post hoc test for multiple comparisons [F_(2,18) = 11.64; p = 0.0006; control(APP KO) vs eAβos, p = 0.0041; control(APP KO) vs eAβos (APP KO), p = 0.0008] for NMDA sEPSC frequencies. *p < 0.05, **p < 0.01, ***p < 0.001; #p < 0.05, ##p < 0.01 relative to the T₀ recording normalized to 100%.