MRS2179 restores hippocampal LTP in APPPS1 mice. (A) Representative sample traces before and after LTP of CA3-CA1 Schaffer collateral synapses, and time courses of normalized fEPSP slopes during LTP, in slices perfused with ACSF from APPPS1 mice (red, n = 8 slices from three animals; age, 8 mo) compared with age-matched WT littermates (blue, n = 12 slices from three animals). (B) LTP, quantified as the fEPSP slope potentiation 35–40 min after TBS, was strongly reduced in APPPS1 (transgenic [Tg]) compared with WT mice (*, P < 0.05, Mann–Whitney test). (C) The strength of basal synaptic transmission, assessed by quantifying the baseline fEPSP slope, was reduced in APPPS1 compared with WT mice (*, P < 0.05, Mann–Whitney test). (D–F) LTP and basal synaptic transmission in slices from WT and APPPS1 animals were not significantly different in the presence of MRS2197 (30 µM; red, APPPS1, n = 8 slices from four animals; age, 8 mo; blue, age-matched WT, n = 11 slices from three animals; Mann–Whitney test for both comparisons). The effect of MRS2179 on WT slices was nonsignificant compared with ACSF-perfused slices (P = 0.31, Mann–Whitney test). All data are represented as mean ± SEM.