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).