Figure 10. LLH reduction with GABA_B/sAHP antagonists reduces LFS efficacy.

Trains of 15 min 1 Hz LFS trains were applied to the VHC of bilateral hippocampi–VHC slices after recording baseline epileptic activity extracellularly from CA3/CA1 bilaterally for at least 15 min as shown in Fig. 1B in either (1) 4-AP only (100 μm); (2) CGP-55845-HCl (1 μm) + 4-AP; (3) UCL-2077 (10 μm) + 4-AP; or (4) CGP-55845-HCl + UCL-2077 + 4-AP. The average percentage of seizure reduction during LFS was quantified for left and right hippocampi in each solution (n= 32, 16, 16 and 12 for: 4-AP only; CGP55854 + 4-AP; UCL-2077 + 4-AP; and CGP-55845-HCl + UCL-2077 + 4-AP, respectively.) There are significant differences in average percentage seizure reduction during LFS between groups (P < 0.0001 using ANOVA). CGP-55845-HCl and UCL-2077, as well as their combination, reduce LFS efficacy relative to that in 4-AP alone. Furthermore, the addition of both CGP-55845-HCl and UCL-2077 to 4-AP reduces LFS efficacy significantly more than either one alone as determined using Tukey-Kramer post hoc analysis. Bar graphs represent data means ± SD. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.