Late application of mGlu1 antagonists fails to reverse established long-term synaptic depression (LTD). Test pulses of glutamate were applied to two nonoverlapping sites on the Purkinje cell dendrite. Pulses were alternated at 10-s intervals. To induce LTD, at t = 0 min, six, 3-s-long depolarizing commands to 0 mV were coupled with glutamate pulses delivered only to the paired pathway at t = 0 min. The control pathway received only somatic step depolarization at t = 0 min. Alternate test pulses were then resumed for the duration of the experiment. Early bath application of drug was given from t = −10 to +5 min as indicated by the black horizontal bar. Late bath application of drug, which occurred in separate groups, was given starting at t = 70 min as indicated by the gray horizontal bar. Exemplar traces are single (unaveraged) responses, and they correspond to the points indicated on the time-course graph. Plot points indicate the means ± SE in this and all subsequent graphs; JNJ-16259685 (50 nM) early, n = 7; JNJ-16259685 (50 nM) late, n = 9; LY-456236 (2 μM) early, n = 7; LY-456236 (2 μM) late, n = 8. Scale bars = 2 s, 50 pA.