GPER1 activation and proteasome activity are required for mGluR-LTD in CA3. Hippocampal slices were incubated with DMSO or G1 for 1 h and then treated with DHPG for 15 min, unless otherwise stated. Treatment with rapamycin or MG132 was performed 20–30 min before G1 or DHPG application, respectively. (A) Rapamycin and MG132 blocked LTD induced by G1+DHPG in CA3. DHPG alone (100 µM, 10 min) did not induce LTD in CA3. (B) Traces (top) and averaged values of slopes (bottom) of fEPSPs measured in CA3 50 min after DHPG application. Bar, 0.5 mV/5 ms. ***, P < 0.001 versus control; ##, P < 0.01 versus G1+DHPG (n = 3, one-way ANOVA). (C) Representative images of double immunostaining for GluA1 (red) and PSD95 (green) under various experimental conditions. High-magnification images correspond to the CA3 pyramidal layer. Bars: (4×) 400 µm; (20×) 100 µm; (100×) 20 µm. (D–F) Quantification of GluA1 immunostaining by means of total area and mean fluorescence intensity (MFI) in CA1 (D) and CA3 (E and F). *, P < 0.05 versus control; #, P < 0.05 versus G1+DHPG (n = 4–10, one-way ANOVA). Error bars indicate means ± SEM.