mGluR II agonists induce LTD at GABAergic synapses. A, B, Individual IPSCs recorded once every 30 s varied widely in amplitude, but the averaged amplitude remained relatively constant in 80-min recordings (n = 8). C, D, Bath-application of an mGluR II agonist DCG-IV (4 μm) induced an initial transient suppression, followed by LTD of IPSCs (n = 14). E, LY341495 (3 μm), an antagonist for mGluR II, eliminated the effects of DCG-IV (n = 7). F, Another mGluR II agonist, LY354740 (1 μm), also induced an initial transient suppression and LTD of IPSCs (n = 7). G, H, mGluR I agonist (3,5-DHPG, 200 μm; n = 5) or mGluR III agonist (l-AP-4, 10 μm; n = 7) produced an initial suppression but not LTD of IPSCs in NM neurons. I, LY341495 (3 μm) slightly increased the amplitude of IPSCs evoked at 0.03 Hz (n = 8). J, Application of LY341495 (3 μm) during the induction of LTD partially reversed the plasticity (n = 16), suggesting the presence of a low level of tonic inhibition mediated by ambient glutamate-activated mGluR II. K, Averaged amplitude of IPSCs under the conditions of LY341495 (I), DCG-IV (D), and LY341495 during LTD induction (J), normalized to their respective controls. The red dashed lines indicate the baseline (100% of control). Cells were voltage clamped at −70 mV. Means ± SEM are shown in this and subsequent figures. *p < 0.05 (t test).