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. 2021 Aug 18;7:76. doi: 10.1038/s41531-021-00210-w

Fig. 3. α-Synuclein overexpression reduces D2 receptor autoinhibition.

Fig. 3

a Representative images of naive dopaminergic neurons (top) and α-syn-overexpressing dopaminergic neurons (bottom); before (left) and during dopamine (1 μM) administration (right). b (Top) In naive neurons, dopamine reduced the ∆F/FGCaMP6f (n = 14–21, two-way ANOVA, p = 0.0003, from five independent replicates). (Bottom) In α-syn-overexpressing neurons, dopamine produced a smaller reduction in ∆F/FGCaMP6f (n = 17–26, two-way ANOVA, p = 0.0088, from five independent replicates). c The fold change in ∆F/FGCaMP6f before and after (n = 11–17, two-tailed t test, p = 0.0031, from five independent replicates). d Representative images of naive dopaminergic neurons (top) and α-syn-overexpressing neurons (bottom), before (left) and after quinpirole (10 μM) (right). e In naive neurons, quinpirole reduced the ∆F/FGCaMP6f (top panel) (n = 11–21, two-way ANOVA, p = 0.0007, from five independent biological replicates). In α-syn-overexpressing neurons, quinpirole produced a smaller reduction in ∆F/FGCaMP6f (bottom panel) (n = 13–26, two-way ANOVA, p = 0.7259, from five independent replicates). f Fold change in ∆F/FGCaMP6f before and after drug (n = 11–13, two-tailed t test, p = 0.0217, from five independent replicates). g (Top left) A representative recording of the spontaneous firing activity of naive dopaminergic neurons before and during quinpirole (10 μM) (n = 6, from three independent biological replicates). (Top right) A representative recording of the spontaneous firing activity of α-syn-overexpressing neurons before and during quinpirole (10 μM) (n = 8, from three independent experiments). (Bottom) Acute quinpirole treatment significantly increases raw interspike interval distributions of naive and α-syn-overexpressing dopaminergic neurons (Kolmogorov–Smirnov test, naive—D = 0.50642, p < 0.001, α-syn overexpressing—D = 0.47776, p < 0.001). h Comparison of the firing frequency of naive (black) and α-syn-overexpressing neurons (pink bar) during quinpirole administration (green) (n = 7 from independent experiments, two-way ANOVA, p = <0.0001). i Interspike interval—n = 7 from independent experiments, two-way ANOVA, p = 0.0136; j firing regularity (CV of ISI)—n = 7 from independent experiments, two-way ANOVA, p = 0.0200). The data are presented as mean ± SEM. h, i are presented as %change from untreated naive. Scale bar = 50 μm. *p < 0.05, **p < 0.01.