Fig. 3. MEK inhibitors suppress low-frequency, but not high-frequency, stimulation-induced LTP. A, The amount of LTP induced by 30 sec of 5 Hz stimulation (delivered at time0) in slices continuously bathed in 20 μmU0126 (filledsymbols; fEPSPs were 122.2 ± 5.1% of baseline; n = 6) was reduced significantly (p < 0.01) as compared with that seen in interleaved vehicle control experiments (open symbols; 0.2% DMSO; fEPSPs were potentiated to 167.7 ± 9.9% of baseline; n = 5). B, Summary of the effects of three different MEK inhibitors on 5 Hz stimulation-induced LTP. Values show the amount of LTP present 40–45 min after 5 Hz stimulation. Similar amounts of LTP were induced by 5 Hz stimulation in interleaved vehicle control experiments (0.1–0.33% DMSO; n = 17), and the combined results are shown by the open bar. Results for U0126 are from the same experiments shown in A. fEPSPs in PD98059 (PD)-treated slices were 109.9 ± 9% of baseline (n = 5) after 5 Hz stimulation (**p < 0.01 compared with 0.33% DMSO control experiments), whereas fEPSPs were 118.4 ± 13.4% of baseline (n = 7) after 5 Hz stimulation in SL327 (SL)-treated slices (*p < 0.05 compared with 0.1% DMSO control experiments). In interleaved control experiments the fEPSPs were 155.1 ± 5.9% of baseline (0.33% DMSO; n = 5) and 165.1 ± 17.4% of baseline (0.1% DMSO; n = 7), respectively.C, High-frequency stimulation-induced LTP is not inhibited by U0126. Two 1-sec-long trains of 100 Hz stimulation (intertrain interval, 10 sec; delivered at time 0) induced similar amounts of LTP in vehicle control experiments (0.2% DMSO; open symbols; n = 6) and in slices continuously bathed in 20 μm U0126 (filled symbols; n = 5). In control experiments 55–60 min after 100 Hz stimulation the fEPSPs were potentiated to 185.9 ± 20.5% of baseline, whereas in U0126-treated slices the fEPSPs were 188.7 ± 43.2% of baseline.D, Summary of the effects of MEK inhibitors on 5 Hz stimulation-induced complex spike bursting. The plot shows the percentage of EPSPs during the 5 Hz stimulation train that evoked complex spike bursts (CSB, defined as two or more negative-going spikes after EPSP onset; see Thomas et al., 1998) in vehicle control experiments (left) and in the presence of MEK inhibitors (right). Measurements were taken from the experiments shown in B. Although complex spike bursting tended to be reduced in slices pretreated with MEK inhibitors, none of the inhibitors produced a statistically significant suppression of complex spike bursting when compared with interleaved vehicle control experiments (PD98059 vs 0.33% DMSO controls:t(8) = 1.78, p = 0.11; U0126 vs 0.2% DMSO controls:t(9) = 1.16, p = 0.28; SL327 vs 0.1% DMSO controls:t(11) = 1.12, p = 0.29).