FIGURE 7.

Activation of GABA_BRs by baclofen suppresses fEPSP_slope more in the ventral than in the dorsal hippocampus and prolongs fEPSP_τ more in the dorsal than in the ventral hippocampus. Collective time courses of percent change of fEPSP_slope and fEPSP_τ illustrating the action of baclofen in the dorsal hippocampus and the ventral hippocampus are shown in panels (A,B), respectively. In collective diagrams, values shown below and above zero correspond to changes in fEPSP_slope and fEPSP_τ, respectively. The number of slices studied is shown into parenthesis in collective graph legends. Data for 0.5 μM (fEPSP_slope) and 50 μM (fEPSP_slope and fEPSP_τ) are not shown in collective graphs for clarity reasons. Representative examples of fEPSP traces, shown on the top of graphs, were collected under control conditions and under 5 or 50 μM baclofen. Calibration bars: 0.5 mV, 5 ms. Note that 5 μM baclofen suppresses fEPSP_slope more in the ventral than in the dorsal hippocampus and at the same time prolongs the decay phase of fEPSP in the dorsal but not the ventral hippocampus. Also note that a 5 min application of 50 μM baclofen induces an increase in fEPSP decay phase in the dorsal but not the ventral hippocampus, i.e., before any change in fEPSP_slope occurs (blue trace, baclofen 5 min). (C) Concentration-effect curves for baclofen actions on fEPSP_slope. Curves were constructed using the Boltzmann function. The number of slices used is indicated in the legend. Dotted arrowed lines indicate EC₅₀ values for the ventral (VH, 2.57 μM) and the dorsal hippocampus (DH, 5.98 μM). The two curves differ significantly (non-linear regression analysis, p < 0.0001). (D) Concentration-effect relationship of baclofen actions on fEPSP_τ. The number of slices used for all baclofen concentrations, but 50 μM, is shown in panel (B); the effects of 50 μM baclofen were studied in eight dorsal and five ventral hippocampal slices. (E) Graph of cumulative time courses of baclofen-induced changes in fEPSP_slope and fEPSP_τ (suppression and enhancement, respectively) in the dorsal and the ventral hippocampus, constructed by pooling data from all baclofen concentrations. Lines on both sides of symbols indicate SEM. The number of slices studied in given into parenthesis. Arrow depicts the start of baclofen application (time = 0), which continues for the next 30 min. The inset graph on the top-left of panel shows the mean values of fEPSP_τ under control and drug conditions. Asterisks indicate statistically significant differences at p < 0.05 (paired t-test and independent t-test were used for comparisons inside and between hippocampal segments, respectively). Note that under control conditions the value of fEPSP_τ is higher in the ventral than in dorsal hippocampus; following baclofen application the value of fEPSP_τ becomes similar in the two hippocampal segments. The inset graph on the bottom-left of the panel shows that baclofen-induced suppression of fEPSP_slope was significantly higher in the ventral than in dorsal hippocampus (asterisk, independent t-test, p < 0.05). (F) Are shown time course diagrams (graph on the left), example traces of fEPSP recordings (upper-right panel) and aggregate data under control and drug conditions (lower-right graphs) illustrating that 10 μM CGP52432 fully reversed the effects of 20 μM baclofen on fEPSP_slope and fEPSP_τ in the dorsal and the ventral hippocampus. Horizontal lines indicate statistically significant differences; the level of significance is also given. Calibration bars: 0.5 mV, 5 ms.