Figure 6. AMPA EPSC facilitation by synaptically released zinc is frequency, history, and Pr dependent. A, B, Upper panels, representative traces of AMPA EPSCs evoked by 20-pulse train at 5 Hz (A) and 20 Hz (B), before (gray) and after (color) 100 µM ZX1, in 2.4 mm external calcium. Lower panels, summary graphs showing average AMPA EPSC amplitudes during the 20-pulse train, normalized to EPSC amplitude of the first pulse, before (gray) and after (color) ZX1 application at 5 Hz (A) and 20 Hz (B), in 2.4 mm external calcium (ratio of the amplitude of 16–20 EPSC to first EPSC: 2.4 mm calcium: 5 Hz: control vs. ZX1, n = 5, p = 0.58; 20 Hz: control vs. ZX1, n = 5, p = 0.09). C–E, Upper panels, representative traces of AMPA EPSCs evoked by 20-pulse train at 5 Hz (C), 20 Hz (D), and 50 Hz (E), before (gray) and after (color) 100 µM ZX1, in 1.2 mm external calcium. Lower panels, summary graphs showing average AMPA EPSC amplitudes during the 20-pulse train, normalized to EPSC amplitude of the first pulse, before (gray) and after (color) ZX1 application at 5 Hz (C), 20 Hz (D), and 50 Hz (E) in 1.2 mm external calcium (ratio of the amplitude of 16–20 EPSC to first EPSC: 1.2 mm calcium: 5 Hz: control vs. ZX1, n = 5, p = 0.34; 20 Hz: control vs. ZX1, n = 5, p = 0.45; 50 Hz vs. ZX1, n = 10, p < 0.01). F, G, Upper panels, representative traces of AMPA EPSCs evoked by 50-Hz 20-pulse train, before (black) and after (color) 100 µm ZX1, in ZnT3WT (F) and ZnT3KO (G) mice. Lower panels, summary graphs showing average AMPA EPSC amplitudes during the 50-Hz 20-pulse train, normalized to EPSC amplitude of the first pulse, before (black) and after (color) ZX1 application, in ZnT3WT (F) and ZnT3KO (G) mice (ratio of the amplitude of 16–20 EPSC to first EPSC: ZnT3WT mice: 50 Hz control vs. ZX1, n = 6, p < 0.01; ZnT3KO mice: 50 Hz: control vs. ZX1, n = 5, p = 0.85). H, Upper panel, representative traces of peak-scaled AMPA EPSCs evoked by 50-Hz 20-pulse train in ZnT3WT (black) and ZnT3KO mice (green). Lower panel, summary graphs showing average AMPA EPSC amplitudes during the 50-Hz 20 pulse train, normalized to EPSC amplitude of the first pulse in control conditions, in ZnT3WT (black) and ZnT3KO (color) mice (ratio of the amplitude of 20 EPSC to first EPSC: ZnT3WT vs. ZnT3KO: control: 50 Hz, n = 5, p < 0.01). Values represent mean ± SEM. Detailed values and statistical tests: A, B, lower panels: ratio of the amplitude of 16–20 EPSC to first EPSC: 2.4 mm calcium: 5 Hz: control: 1.40 ± 0.12 vs. ZX1: 1.34 ± 0.15, n = 5, p = 0.58, F = 0.31, DFn = 1, DFd = 40; 20 Hz: control: 2.03 ± 0.09 vs. ZX1: 1.83 ± 0.14, n = 5, p = 0.09, F = 3.0, DFn = 1, DFd = 40; two-way ANOVA. C–E, lower panels: ratio of the amplitude of 16–20 EPSC to first EPSC: 1.2 mm calcium: 5 Hz: control: 1.54 ± 0.14 vs. ZX1: 1.61 ± 0.11, n = 5, p = 0.34, F = 0.9, DFn = 1, DFd = 40; 20 Hz: control: 2.78 ± 0.29 vs. ZX1: 2.94 ± 0.34, n = 5, p = 0.45, F = 0.56, DFn = 1, DFd = 40; 50 Hz: 4.44 ± 0.47 vs. ZX1: 3.14 ± 0.37, n = 10, p < 0.01, F = 22.59, DFn = 1, DFd = 90; two-way ANOVA. F, G, lower panels: ratio of the amplitude of 16–20 EPSC to first EPSC: ZnT3WT mice: 50 Hz: 5.580 ± 0.39 vs. ZX1: 3.96 ± 0.55, n = 6, p < 0.01, F = 28.37, DFn = 1, DFd = 50; ZnT3KO mice: control: 50 Hz: 1.71 ± 0.27 vs. ZX1: 1.74 ± 0.33, n = 5, p = 0.85, F = 0.04, DFn = 1, DFd = 40; two-way ANOVA. H, lower panel: ratio of the amplitude of 16–20 EPSC to first EPSC: ZnTWT vs. ZnT3KO: control: 50 Hz: 5.58 ± 0.39 vs. 1.71 ± 0.27, n = 5, p < 0.01, t = 8.15, df = 8; unpaired t-test.