Impairment of DHPG-LTD in young IP₃K-A Tg mice.

<p>(A), Induction and expression of DHPG-LTD. Top plot, DHPG-LTD was significantly inhibited in IP₃K-A Tg mice compared with WT (measured at 61–70 min (grey bar); WT, 86.5 ± 0.1% of baseline, n = 20 slices; Tg, 97.7 ± 0.4%, n = 18 slices; ***<i>p</i> < 0.001). Middle plot, the mean PPF ratio of the baseline of Tg mice was significantly lower than that of WT (WT, 1.69 ± 0.34E-2; Tg, 1.61 ± 0.38E-2; ***<i>p</i> < 0.001). Bottom plot, The normalized PPF ratio after DHPG washout was significantly reduced in Tg mice compared with that of WT (measured at 61–70 min (grey bar); WT, 0.93 ± 0.20E-2; Tg, 0.81 ± 0.42E-2; ***<i>p</i> < 0.001). (B), DHPG-LTD in Rö-31-8220 pre-incubated slices. 1 μM Rö-31-8220 was applied throughout the entire recording period. Top plot, DHPG (50 μM) application for 10 min induced LTD in CA1 synapses in WT and Tg mice (measured at 61–70 min; WT, 83.9 ± 0.3% of baseline, n = 14; Tg, 81.4 ± 0.3%, n = 15). Middle plot, the mean PPF ratio of the baseline of Tg mice was significantly higher than that of WT (WT, 1.58 ± 0.25E-2; Tg, 1.70 ± 0.18E-2; ***<i>p</i> < 0.001). Bottom plot, normalized PPF ratio after DHPG washout was significantly reduced in both WT and Tg mice (measured at 61–70 min; WT, 0.75 ± 0.01; ***<i>p</i> < 0.001; Tg, 0.80 ± 0.01; ***<i>p</i> < 0.001). (C), DHPG-LTD in calphostine C pre-incubated slices. 1 μM calphostin C was applied throughout the entire recording period. Top plot, DHPG (50 μM) application induced LTD in CA1 synapses in WT and Tg mice (measured at 61–70 min; WT, 77.3 ± 0.2% of baseline, n = 6, <i>p</i> < 0.001; Tg, 80.0 ± 0.7%, n = 6, <i>p</i> < 0.001). Middle plot, themean PPF ratio of the baseline of Tg mice was similar to that of WT (WT, 1.63 ± 0.30E-2; Tg, 1.66 ± 0.02E-2; <i>p</i> < 0.001). Bottom plot, After DHPG washout, the normalized PPF ratio was almost unchanged compared to the baseline of WT and Tg mice (measured at 61–70 min; WT, 1.00 ± 0.01; Tg, 0.97 ± 0.01; <i>p</i> = 0.004). (D), DHPG-LTD in 2-APB pre-incubated slices. 16 μM 2-APB was applied throughout the entire recording period. Top plot, DHPG (50 μM) application did not induce LTD in CA1 synapses in WT and Tg mice (measured at 61–70 min; WT, 101.0 ± 0.5% of baseline, n = 18; Tg, 98.8 ± 0.3%, n = 20). Middle plot, the mean PPF ratio of the baseline of Tg mice was similar to that of WT (WT, 1.57 ± 0.40E-2; Tg, 1.55 ± 0.16E-2; <i>p</i> < 0.001). Bottom plot, the normalized PPF ratio after DHPG washout was reduced compared with that of baseline in WT and Tg mice (measured at 61–70 min; WT, 0.74 ± 0.78E-2; <i>p</i> < 0.001; Tg, 0.83 ± 0.39E-2, <i>p</i> < 0.001). Inlet traces are sample traces at scale of 0.5 mV/8 msec. All inlet traces are sample traces. Scale bars: 0.8 mV, 8 msec. (E), Summary plot of basal PPF ratio data before and after drug treatments shown in (A–D). (F), Summary plot of normalized PPF ratio data at 61–70 min period after DHPG-LTD induction shown in (A–D).