Fig. 3: Parvalbumin-interneurons mediate SNCA-associated motor learning deficits. | Communications Biology

Fig. 3: Parvalbumin-interneurons mediate SNCA-associated motor learning deficits.

From: Human α-synuclein aggregation activates ferroptosis leading to parvalbumin interneuron degeneration and motor learning impairment

Fig. 3

a Coronal sections of mouse M1 for SNCA expression and parvalbumin-interneurons (PV-INs). Scale bar, 100 μm. b SNCA-overexpressed mice had remarkably decreased density of PV-INs. Two-sample unpaired t-test, t(10) = 5.491, P = 0.0003. N = 6 mice in each group. c Fluorescent staining for the wisteria floribunda agglutinin (WFA) as the marker of perineuronal nets around PV-INs. Scale bar, 100 μm. d Experimental design for in vivo calcium recording of PV-INs via Cre-mediated GCaMP6s expression on PV-Cre mice. e Sample traces of calcium transients of PV-INs from both groups. f Comparison of total integrated calcium signal strength showed decreased activities in the SNCA group. Non-parametric Kolmogorov–Smirnov test, D = 0.2557, P = 0.0009. g The frequency of calcium transients was also depressed in the model group. Non-parametric Kolmogorov–Smirnov test, D = 0.3480, P < 0.0001. n = 134 and 105 neurons from 4 mice of mCherry and SNCA groups, respectively, in (f, g). h Illustration for experimental procedures of rescuing assay, in which excitatory hM3Dq under Cre-dependent expression was introduced into PV-IRES-Cre mice, followed by 2-week CNO administration and motor learning phenotyping. i Representative immunofluorescent staining for cFos activity. Scale bar, 100 μm. j cFos activity was reduced by CNO treatment. Two-sample unpaired t-test, t(6) = 12.52, P < 0.0001. N = 4 mice in each group. k Chemogenetic activation of cortical PV-INs improved motor learning abilities on the rotarod. Two-way ANOVA with respect to group factor, F(1126) = 43.38, P < 0.0001. Sidak’s multiple comparison test of post hoc comparison at each time point. l PV-INs excitation conferred better performance on vertical pole climbing. Two-way ANOVA with respect to group factor, F(142) = 21.66, P < 0.0001. Sidak’s multiple comparison test of post hoc comparison at each time point. m The reaction of PV-INs also enhanced the acquisition of beam walking abilities. F(142) = 19.78, P < 0.0001. Sidak’s multiple comparison test of post hoc comparison at each time point. N = 7 and 9 mice in saline and CNO group, respectively, in (k–m). ***P < 0.001. All data were presented as mean ± SEM.

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