Introduction of Notch1 ICD rescues the phenotypes of mib1 cKO mice. (A) Schematic drawing of mouse breeding. RN1;mib1 cKO mice were generated by crossing CaMKII-cre/+;mib1f/f mice with the Rosa-Notch1/+; mib1f/f mice. (B, C) Increased pkm ζ and Notch target genes in the RN1;mib1 cKO mice. Total RNA and protein lysates from the hippocampus of 4-month-old wild-type (n = 4) and RN1;mib1 cKO mice (n = 4) were analyzed by quantitative real-time PCR (left panel) (B) and by western blotting (C). PKMζ protein levels were quantified by densitometry (right panel). (D) Normal synaptic transmission in mib1 cKO and RN1;mib1 cKO mice. The synaptic input–output relationship was obtained by plotting the initial slope against the stimulus intensity (n = 8 for WT, n = 8 for cKO, n = 10 for RN1;mib1 cKO). (E) Normal paired-pulse response ratio in mib1 cKO and RN;mib1 cKO mice. The graph depicts the paired-pulse response ratio (2nd fEPSP/1st fEPSP) obtained at different interstimulus intervals (n = 7 for WT, n = 7 for cKO, n = 11 for RN1;mib1 cKO). (F) L-LTP is totally recovered in RN;mib1 cKO mice compared to mib1 cKO mice (n = 8 for WT, n = 10 for cKO, n = 7 for RN1;cKO).