Fig. 8: Enhanced tonic inhibition of striatal DA release and impaired GAT function in mouse model of early parkinsonism.
a, b, e, i Mean peak [DA]o during consecutive recordings evoked by a single (1p) light (a, b, i) or electrical pulse (e) in DLS (a, e, i) or NAcC (b) during applications of antagonists for GABAA (bicuculline, 10 µM) and GABAB receptors (CGP 55845, 4 µM) (a, b, i), or the nonspecific GAT inhibitor NPA (1.5 mM) (e) in slices preincubated (i) or not preincubated (a, b, e) with fluorocitrate (FC, 200 µM, 45–60 min) from Snca−/− (dark blue, GABAR antagonism: n = 7 experiments/5 mice in DLS (a), n = 9 experiments/5 mice in NAcC (b), n = 7 experiments/3 mice for fluorocitrate (i); NPA: n = 5 experiments/4 mice (e) and SNCA+ mice (light blue, GABAR antagonism: n = 8 experiments/5 mice for both DLS and NAcC (a, b), n = 6 experiments/3 mice for fluorocitrate (i); NPA: n = 5 experiments/4 mice (e). Data are normalized to mean of four timepoints prior to drug application (dotted line); mean transients of [DA]o are derived from last four timepoints (grey shaded region) and normalized to predrug baselines. c, d, f, g, j, k Cumulative frequency plots of individual data points (c, f, j) and mean per recording site (d, g, k) from a, b, e, i. h Representative Western blots and mean GAT-1 and GAT-3 protein content of dorsal striatum tissue taken from Snca−/− mice (n = 10 mice) and SNCA+ mice (n = 7 mice). Data normalized to actin and littermate control expression. Two-way repeated-measures ANOVA with Sidak’s multiple comparison tests (a, b, e, i), Komogorov–Smirnov tests (c, f, j), two-tailed Student’s unpaired t-tests (d, g, k) and Mann–Whitney U tests (h). *p < 0.05, **p < 0.01, ***p < 0.001. Error bars are ±SEM. Source data and uncropped blots from h are provided as a Source Data file.
