Figure 1.
Chronic PFE-360 treatment slightly normalizes motor function but not STN burst firing induced by AAV-α-synuclein overexpression. A, Motor symmetry assessed nine weeks after intracerebral viral inoculation of AAV-α-synuclein or CTRL (empty AAV-vector). The test was performed 1–2 h after dosing (one-way ANOVA, p < 0.001; CTRL veh and PFE-360 N = 6, α-syn veh and PFE-360 N = 5). B, Locomotor activity measured 5–7 h after dosing revealed a non-significant trend for a decreased activity in α-synuclein overexpressing rats in both treatment groups compared to CTRL rats. PFE-360 treatment did not have any adverse effect on locomotion in the CTRL group (one-way ANOVA, p = 0.51; CTRL veh and PFE-360, N = 6, α-syn veh and PFE-360, N = 5). C, Representative action potential and spike-trains from single unit recordings of putative glutamatergic neuron in the STN. The spike-trains are representative examples of regular (top), irregular (middle), and bursty (bottom) firing patterns. D, CV ISI is increased by α-synuclein overexpression in both treatment groups (Kruskal–Wallis test, p < 0.001). E, Proportional distribution of regular, irregular and bursty neurons (χ2 = 22.28, df = 6, p = 0.0011) shows increased proportion of bursty neurons in α-synuclein overexpressing rats in both treatment groups. F, The average firing rate of STN neurons is not significantly different between groups (Kruskal–Wallis test, p = 0.11). D–F, N: number of animals; n: number of neurons; CTRL veh (N = 5, n = 98), α-synuclein veh (N = 6, n = 99), CTRL PFE-360 (N = 6, n = 90), and α-synuclein PFE-360 (N = 6, n = 113). Tukey’s multiple comparison is represented by the lines; *p < 0.05, **p < 0.01, ***p < 0.001. For multiple χ2 tests in (E) the Bonferroni-corrected p value was used, *p < 0.0125 (four comparisons: significance level, p = 0.0125).