Adult KO mice present a higher susceptibility to vHP-LFS induced LTD. A, Representative experiment illustrating time course of mPFC-evoked response before and after LFS 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) LFS stimulation. The LFS protocol induces a long-lasting depression of the evoked response. Response amplitudes were normalized to mean baseline amplitude. B, mPFC response amplitude recorded from animals subjected to successive LFS protocols. Juvenile control and KO mice showed similar levels of LTD after application of successive LFS protocols (two-way repeated-measures ANOVA: genotype factor, p = 0.68; genotype × time interaction, p = 0.35). Adult KO mice presented greater levels of induced LTD than control mice (two-way repeated-measures ANOVA: genotype × time interaction, p < 0.01). *p < 0.05 (Newman-Keuls post hoc test). Each point represents mean ± SEM of n animals. C, The mPFC-evoked response is smaller after each of the LFS protocols in adult, but not in juvenile, NMDAR-KO. Statistical analysis combining genotype, age, and LFS repetition was conducted by three-way repeated-measures ANOVA (genotype × age interaction, p = 0.035). *p < 0.05 (Newman-Keuls post hoc test vs adult control). Error bar indicates mean ± SEM. Each dot represents the response measured in 1 individual animal. n.s., not significant.