PERK is required for the distinct regulation of eIF2α phosphorylation following mGluR-LTD induction. (A) E-LTP and L-LTP stimulation decreases eIF2α phosphorylation in hippocampal area CA1. Untetanized (control) slices vs. 1 × 100 Hz (E-LTP) and 4 × 100 Hz (L-LTP) slices are compared (n = 5 slices per condition, [*] P < 0.05, [**] P < 0.01, one-way ANOVA). (B) DHPG application (50 µM, 10 min) increases eIF2α phosphorylation in hippocampal area CA1 (n = 6 slices per condition, [*] P < 0.05, Student's t-test). (C) The DHPG-induced increase in eIF2α phosphorylation in WT slices is blocked in PERK cKO slices. Hippocampal slices from PERK cKO and WT mice were treated with or without DHPG (50 µM, 10 min, n = 6 slices per condition, [*] P < 0.05, one-way ANOVA). (D) mGluR1 and mGluR5 expression were unaltered in hippocampal lysates from PERK cKO mice compared to wild-type littermates (mGluR1, n = 4, P = 0.6; mGluR5, n = 6, P = 0.8, Student's t-test). Representative Western blots are shown in each panel.