Figure 2.

Strong DP induced by DP8 is blocked by inhibition of NMDAR and facilitated by inhibition of mGluR1. (A) The competitive NMDAR antagonist D-AP5 (50 μM; n = 6) caused a significant reduction in the magnitude of DP when compared to vehicle experiments (DP8 only; n = 8). Error bars represent SEM, p = 0.009. (B) While bath application of the selective mGluR5 antagonist MPEP (40 μM; n = 7) had no significant effect on DP, the mGluR1 inhibitor YM 298198 (1 μM; n = 7) caused a significant enhancement in the magnitude of LTP reversal compared to the vehicle group (DP8 only; n = 7). Error bars represent SEM, p = 0.009. Inset graph shows a series of extended baseline recordings comparing group of slices with YM 298198 application (n = 6) and vehicle application (n = 7). As indicated by almost identical curves, YM 298198 had no effect on basal synaptic transmission. DP8′ application is indicated by the filled box above the plot; arrow indicates time of TBS application. Traces show representative examples of fEPSPs recorded during baseline (black line), 1 min post-TBS induction (black broken line), 1 min post-LFS (gray broken line) and 120 min post-TBS (gray line). Calibration bars: 0.5 mV and 5 ms. See Figure 1 for further explanation. (C) The combined application of D-AP5 and YM 298198 resulted in a significant enhancement of DP (p < 0.010 RM-ANOVA, n = 6; control n = 9) which is, however, very similar to the effects of applying YM 298198 alone (shown in panel B; main group effect from 15 min to 120 min post LFS induction: p = 0.2406, RM-ANOVA); same data for vehicle (DP8) as in Figure 1C. (D) Bath-application of MK-801 (10 μM, n = 7 and 100 μM, n = 6) or high Mg²⁺ (10 mM, n = 6) did not inhibit DP and resulted in values at the level of controls (n = 9). These findings support a metabotropic operation of NMDAR during DP8′. **p ≤ 0.01.