Adult KO mice exhibit normal susceptibility to vHP-HFS induced LTP. A, Representative experiment illustrating time course of mPFC-evoked response before and after HFS stimulation of vHP. Each dot represents amplitude of the response evoked by a test pulse delivered to vHP. Inset, Traces of mPFC-evoked responses before (black) and after (gray) HFS stimulation. The LTP protocol induces a long-lasting potentiation of the evoked response. Response amplitudes were normalized to mean baseline amplitude. B, mPFC response amplitude recorded from animals subjected to successive HFS protocols. A higher susceptibility to HFS in juvenile KO mice results in a significant increase in the evoked response compared with control mice after application of successive HFS pulse trains (two-way repeated-measures ANOVA: genotype × time interaction, p < 0.0001). *p < 0.05 (Newman-Keuls post hoc test vs adult control). Each point represents mean ± SEM of n animals. In contrast, adult control and KO mice showed no significant differences in LTP levels after application of successive HFS protocols (two-way repeated-measures ANOVA: genotype factor, p = 0.79; genotype × time interaction, p = 0.54). C, The mPFC-evoked response is bigger after each of the HFS protocols in juvenile, but not in adult, NMDAR-KO. Statistical analysis combining genotype, age, and LFS repetition was conducted by three-way repeated-measures ANOVA (genotype × age interaction, F_(1,87) = 4.80, p = 0.036; observed power: 0.56). *p < 0.05 (Newman-Keuls post hoc vs juvenile control). Error bar indicates mean ± SEM. Each dot represents the response measured in 1 individual animal. n.s., not significant.