(A) Input-Output curves recorded in the Schaffer collaterals of the hippocampus show that basic synaptic transmission is impaired in Aph1bc+/− heterozygous and homozygous Aph1bc−/− mutant mice as compared to control littermates. Graph shows means ± SEM, RM-ANOVA for the three groups: F(2,18) = 4.163, p<0.05; Ctrl: n = 6; Aph1bc+/−: n = 7; Aph1bc−/−: n = 6. (B) Paired pulse facilitation (PPF), a presynaptic form of short term synaptic plasticity, is not significantly affected by genetic Aph1bc deletion. RM-ANOVA, p>0.05. (C) Long term potentiation elicited by three bursts of theta stimulations (black arrows) is reduced in heterozygous and homozygous Aph1bc mutant mice in comparison to control mice. The insets show representative traces from mutant and control mice. Means ± SEM, RM-ANOVA for the three groups. F(2,18) = 9.74, p=0.0014. Ctrl n = 6; Aph1bc+/− n = 7; Aph1bc−/− n = 6. (D) Representative traces from mEPSC recordings in slices from control, Aph1bc+/− and Aph1bc−/− mice plotted in (E) and (F). (E) Cumulative plot of inter-event intervals of mEPSCs in control, heterozygous and homozygous Aph1bc deficient mice. Kruskal–Wallis test followed by Dunn's multiple comparison test, **p<0.01. Median, Ctrl 1651 ms , BC+/− 1835 ms, BC−/− 1947 ms. Mean, Ctrl 2465 ms ± 56, BC+/− 2550 ms ± 58, BC−/− 2622 ms ± 56. n >1679 each out of 37 control, 36 Aph1bc+/− and 35 Aph1bc−/− neurons. (F) Cumulative probability of mEPSCs amplitude in control and mutant Aph1bc mice. Komolgorov–Smirnov test, p>0.05.