EphA4 redistribution to PSD clusters and LTP impairment is attenuated in SORLA TG mice. (A and B) Hippocampal Aβ injection induces EphA4 redistribution to PSD95 puncta. WT and SORLA TG mice were injected with PBS or Aβ and subjected to immunohistological staining for Aβ (brown) using MOAB-2 antibody (A) or costaining for EphA4 (red) and PSD95 (green; B). DAPI (blue) insets in B depict the dentate gyrus region imaged. Bars: (A) 300 µm; (B) 100 µm. Boxes in A and B are magnified in adjacent panels. EphA4/PSD95 co-staining puncta (yellow) are marked by yellow circles in magified panels in B. (C) Graph indicates percentage of red/green overlapping puncta scored for five 100-µm-square regions from hippocampal sections (mean ± SE; **, P < 0.001; Student’s t test). (D and E) SORLA overexpression restores Aβ-induced LTP impairment. Mean fEPSP slopes normalized over baseline values are shown for WT and SORLA TG acute slices under steady-state conditions with or without 500 nM Aβ as indicated. Baseline recordings were taken 20 min before LTP induction (0 time point), and 60 min after LTP induction. Graph represents mean ± SE; *, P < 0.05. (E) Representative fEPSP recordings obtained before (black) and after (gray) high-frequency stimulation. (F) Cumulative fEPSP slopes between 50 and 60 min after LTP induction (mean ± SE, ≥5 slices per mouse/three mice per genotype/treatment category). Statistical values were calculated using two-way ANOVA; *, P < 0.05.