Figure 1
Z-VAD- fmk and Z-LEHD- fmk rescue the synaptic deficits of FDD KI mice. Vehicle-treated slices from FDDKI mice exhibited a reduction in LTP compared to slices from vehicle-treated WT littermates [WT/vehicle vs. FDD/vehicle: F(1,12) = 27.008, P < 0.0001]. Perfusion with either 10 μM Z-VAD-fmk or 2 μM Z-LEHD-fmk reverses the LTP impairment of FDDKI slices [WT/vehicle vs. FDD/Z-VAD-fmk: F(1,12) = 0.191, P = 0.671. FDD/vehicle vs. FDD/Z-VAD-fmk: F(1,12) = 14.300, P = 0.003. WT/vehicle vs. FDD/Z-LEHD-fmk: F(1,12) = 34.592, P < 0.0001. FDD/vehicle vs. FDD/Z-LEHD-fmk: F(1,12) = 34.592, P < 0.0001] but did not alter normal LTP responses in WT mice [WT/vehicle vs. WT/Z-VAD-fmk: F(1,12) = 0.032, P = 0.861. WT/vehicle vs. WT/ Z-LEHD-fmk: F(1,12) = 0.016, P = 0.900]. Differently, treating slices with 2 μM Z-DEVD-fmk did not overall rescue synaptic plasticity deficits of FDDKI mice [WT/vehicle vs. FDD/Z-DEVD-fmk: F(1,12) = 0.191, P = 0.671. FDD/vehicle vs. FDD/Z-DEVD-fmk: F(1,10) = 4.272; P = 0.063], albeit it delayed the initiation of such deficits. In fact Z-DEVD-fmk rescued the LTP deficit during the initial 45 min of LTP [FDD/vehicle vs. FDD/Z-DEVD-fmk: F(1,10) = 8.93, P = 0.012], but not the deficit occurring during the last 45 min of LTP [FDD/vehicle vs. FDD/Z-DEVD-fmk: F(1,10) = 1.23, P = 0.29]. Of note, Z-DEVD-fmk did not alter LTP in WT mice [WT/vehicle vs. WT/Z-DEVD-fmk: F F(1,10) = 1.968, P = 0.191]. CA1-LTP was induced through a θ burst stimulation of the Shaffer collateral pathway.