PPI deficits in presynaptic mutant mice with abnormal short-term, presynaptic facilitation (RIM1α−/−, Rab3A−/−, Syt1R233Q KI, but not RIM1αS413A KI). a, Significant decrease in prepulse inhibition of acoustic startle in RIM1α−/− mice versus wild-type (WT) littermate controls at all levels of prepulse (4, 8, and 16 dB above background of 70 dB; N = 14 in a–c; two-way mixed ANOVA, main effect of genotype, F(1,26) = 14.35, p < 0.001; main effect of prepulse level, F(2,52) = 35.81, p < 0.001; no significant interaction; p values for post hoc planned comparisons at each prepulse level shown above bars in all panels). b, PPI deficit in Rim1α−/− mice persists even after 4 preceding days of habituation to PPI chambers and background noise before repeat testing (two-way mixed ANOVA; main effect of genotype, F(1,26) = 12.45, p < 0.01; main effect of prepulse level, F(2,52) = 49.56, p < 0.001. c, Significant PPI deficits at all prepulse levels in Rab3A−/− mice versus WT littermate controls (N = 15; two-way mixed ANOVA; main effect of genotype, F(1,26) = 13.08, p < 0.01; main effect of prepulse level, F(2,52) = 43.55, p < 0.001; no significant interaction). d, Significant PPI deficit at prepulse of 8 dB above background noise in Syt1R233Q KI mice versus WT littermate controls (N = 14; two-way mixed ANOVA revealed no significant main effect of genotype, F(1,52) = 3.45, p = 0.07; main effect of prepulse level, F(1,52) = 28.38, p < 0.0001; no significant interaction). Planned comparisons revealed a significant difference only at the 8 dB above background prepulse level (p < 0.05). e, No change in PPI at any prepulse level or in baseline startle in RIM1αS413A KI mice versus WT littermate controls (N = 11; two-way mixed ANOVA, no main effect of genotype, F(1,21) = 0.01, p = 0.94; main effect of prepulse level, F(2,42) = 73.0, p < 0.001; no significant interaction). Error bars indicate mean ± SEM.