Figure 3 . MRS5474 inhibited spontaneous activity in organotypic rhinal-hippocampal slices under depolarizing condition. InA and B representative field potential recordings are shown of spontaneous activity from CA3 area of a control slice (no drug,A ) and of a slice to which MRS5474 (250 nM) was added to the perfusion solution as indicated by the arrow (B ). Upper panel in A and B shows representative recordings during the entire experimental time, while the lower panel shows representative ictal-like discharges in basal conditions in the same slices as in the corresponding upper panel; note that time scale is different in both upper and lower panels. Panels C and D show the mean frequency of spikes within the bursts at the times indicated below each bar; data obtained at 10–20 minutes was in the absence of MRS5474 (basal ictal discharge) and was normalized to 1, whereas data at 50–60 minutes or 80–90 minutes was either in the absence (C ) or in the presence (D ) of MRS5474 (250nM). Data is shown as mean with the dots representing individual data points. Dots from the same experiment are connected by a straight line. Dots corresponding to the experiments represented in A and B are highlighted in blue. In all experiments the concentration of KCl in the perfusion solution was increased to 8.5 mM (depolarizing conditions).* P<0.05; **P<0.01. One-way ANOVA followed by Dunnett’s multiple comparisons test.
Figure 4. MRS5474 decreased fEPSPs in hippocampal slices taken from animals with established epilepsy (EE). MRS5474 application in A an animal with EE or in B a control animal. In the left panels of both A and B are shown representative time-course changes in fEPSP slopes taking as baseline (100%) the values recorded for 10 minutes before drug application. The horizontal lines below drug names indicate drug presence in the perfusion solution. Insets: representative superimposed averaged fEPSPs traces recorded from the same slices as in the panel where they are inserted and at the times indicated by the numbers. In the right panels of both A and B are shown paired EPSP slope values (mV/ms) from all experiments with similar protocols as those shown on the left, in baseline (period 1 indicated on the left panel) and under MRS5474 (period 2 indicated on the left ). Dots corresponding to the experiments represented in A and B are highlighted in red. *P<0.05; ns: P>0.05, two tailed paired t-test).