Alteration of NMDA sEPSCs amplitude in cortical slice neurons by eAβos depends on APP cleavage by γ-secretase and β-secretase. A, Representative traces of NMDA sEPSCs at T₀ and T₂₀ with DAPT (5 μm); with DAPT (5 μm) plus eAβos. B, Bar graphs (mean ± SEM) showing the T₂₀/T₀ ratio of NMDA sEPSCs amplitude and frequency with DAPT (white bars; n = 7 neurons, N = 4 mice, Wilcoxon W = 4(16, −12), p = 0.8125, for sEPSCs amplitude; and Wilcoxon W = −4(12, −16), p = 0.8125, for sEPSCs frequency); with DAPT plus eAβos (gray bars; n = 10 neurons, N = 5 mice, Wilcoxon W = 1(11, −10), p > 0.9999, for sEPSCs amplitude; and Wilcoxon W = −43(6, −49), p = 0.0273, for sEPSCs frequency). DAPT versus DAPT plus eAβos (Mann–Whitney U = 33(61, 92), p = 0.8868, for sEPSCs amplitude; and Mann–Whitney U = 30.5(67.5, 85.5), p = 0.6874, for sEPSCs frequency). C, Representative traces of NMDA sEPSCs at T₀ and T₂₀ with β-secretase inhibitor (1 μm); with β-secretase inhibitor (1 μm) plus eAβos. D, Bar graphs (mean ± SEM) showing the T₂₀/T₀ ratio of NMDA sEPSC amplitude and frequency with β-secretase inhibitor (white bars; n = 6 neurons, N = 4 mice, Wilcoxon W = 1(11, −10), p > 0.9999, for sEPSCs amplitude; and Wilcoxon W = 1(11, −10), p > 0.9999, for sEPSCs frequency); with β-secretase inhibitor plus eAβos (gray bars; n = 8 neurons, N = 3 mice, Wilcoxon W = 12 (24, −12), p = 0.4609, for sEPSCs amplitude; and Wilcoxon W = −36(0, −36), p = 0.0078, for sEPSCs frequency). β-Secretase inhibitor versus β-secretase inhibitor plus eAβos (Mann–Whitney U = 17(38, 67), p = 0.4136, for sEPSC amplitude; and Mann–Whitney U = 5(64, 41), p = 0.0127, for sEPSC frequency). *p < 0.05; #p < 0.05, ##p < 0.01 relative to the T₀ recording normalized to 100%.