(A) Application of the mGlu1/5 agonist DHPG (50 μM) induced long-term depression (LTD) of fEPSP slope (red circles, n=6 slices), while the mGlu2/3 agonist LY379268 (100 nM) had no acute or long-term effects (blue circles, n=5). (B) Co-application of LY379268 abrogated DHPG-induced LTD (pink triangles, n=5). (C) Summary of averaged fEPSP slope of last 5 minutes of recordings from panels A-B (*p<0.05, compared to LY379268 alone, F(2,13)=4.087, one-way ANOVA with Tukey’s post-hoc test). (D) Paired-pulse (PP) 1-Hz stimulation for 15 minutes induces mGlu5-dependent LTD in control slices (grey circles, n=6). Coincidental application of LY379268 (100 nM) changes PP 1-Hz LTD into a long-term enhancement of fEPSP slope (blue circles, n=6). (E) The mGlu3 NAM VU0650786 (VU786; 10 μM) blocked the metaplastic effects of LY379268 application (green diamonds, n=6). (F) Summary of averaged fEPSP slope of last 5 minutes of recordings from panels D and E (***p<0.001, compared to Control, F(2,13)=17.13, p<0.001, one-way ANOVA with Tukey’s post-hoc test). All experiments were performed in presence of mGlu1 NAM, VU0469650 (10 μM). Data are expressed as mean ± SEM.