LFS induces Z-LTP, which requires G1 mGluR activation. A, Time course of AMPAR EPSC amplitude before and after LFS (5 Hz, 3 min), and before and after subsequent ZX1 application (cyan); and similar time course in interleaved control experiments (without LFS, red). LFS did not induce LTD (n = 8, not significant, p = 0.22, paired t test). ZX1 potentiated EPSCs after LFS (n = 6, *p = 0.0025, paired t test) and in controls (n = 5, *p = 0.019, paired t test). B, Time course of AMPAR EPSC amplitude before and after LFS, in the presence of ZX1 (100 μM). LFS induced LTP (n = 5, *p = 0.027, paired t test). C, Similar time course as in A, but with LFS in the presence of LY367385 (100 μM) and MPEP (4 μM) (green), compared with cells with LY367385 and MPEP but without LFS (gray). LFS + LY367385/MPEP did not induce LTD (n = 6, not significant, p = 0.69, paired t test). ZX1 potentiated EPSCs after LFS (n = 6, *p = 0.02, paired t test) and without LFS (n = 6, *p = 0.015, paired t test). A, C, To examine the ZX1 potentiation after LFS, similar approach and renormalization as in Figure 1C were performed. Example traces represent AMPAR EPSCs before and after ZX1. D, Average ZX1 potentiation (% increase from baseline) during the last 5 min of ZX1 application (minutes 21–25). Control: n = 5; LFS: n = 6; LFS + LY367385/MPEP: n = 6; LY367385/MPEP: n = 6. LFS increased ZX1 potentiation compared with control (*p = 0.03); this increase was blocked by LY367385 and MPEP (*p = 0.027); and LFS + LY367385/MPEP was not different from LY367385/MPEP alone (not significant, p > 0.99). One-way ANOVA/Bonferroni. The increase in ZX1 potentiation is termed Z-LTP. E, Time course of AMPAR EPSC amplitude before and after LFS, with and without LY367385/MPEP. After LFS, EPSCs remained stable for the duration of the recording. LFS: n = 4; minutes 19–23 versus minutes 44–48: not significant, p = 0.32, paired t test. LFS + LY367385/MPEP: n = 4, minutes 19–23 versus minutes 44–48: not significant, p = 0.87, Wilcoxon matched-pairs signed rank test.