Figure 4.

HD-related differences in the effect of SNAP5114 on I_Tonic(GABA) and presynaptic depression of evoked GABA release. (A) Sample traces of I_Tonic(GABA) from a Q175 WT and HD SONs. Recordings in the presence of TTX (1 μM), CGP (1 μM), DNQX (10 μM), APV (50 μM), and LY341495 (40 μM). Note opposite effects of GAT-3 block with SNAP5114 (40 μM) in WT and HD. (B) Quantification of results from Q175 WT and HD. Significance level according to 2-Way ANOVA with subsequent Bonferroni correction for four comparisons. Normality was verified by the Kolmogorov–Smirnov test. The ANOVA table gave the following results. Interaction: F_{(1, 41)} = 14.51, p = 0.0005; Genotype: F_{(1, 41)} = 0.0683, p = 0.7951, n.s.; Treatment with SNAP5114: F_{(1, 41)} = 0.4032, p = 0.5290, n.s. (C–E) Experiments in R6/2 WT and HD. Additions: APV 50 μM, DNQX 20 μM, LY341494 40 μM. (C) Records of averaged eIPSCs under the indicated conditions. Note that in WT, but not HD, SNAP5114 removed a presynaptic depressant effect, as indicated by the significant decrease of the PPR (E). Significance levels according to paired t-tests (comparison Control vs. SNAP) and unpaired t-tests (comparison WT vs. HD). The asterisks denote the following: ^*p < 0.05, ^**p < 0.01, and ^***p < 0.001.