Fig. 5: Short-term overexpression of hu-α-Syn in the hippocampus leads to reduced GluA1 AMPA receptors expression and phosphorylation associated with impaired long-term potentiation.

a Western blot analysis of the hippocampal tissue showing that administration of rAAV-hu-α-Syn vector leads to reduced expression of GluA1 (unpaired t test, t = 2.582, P = 0.02, HP-GFP, n = 7; HP-hu-α-Syn, n = 7) and (b) serine 845 phosphorylation (unpaired t test, t = 2.807, P = 0.01, HP-GFP, n = 7; HP-hu-α-Syn, n = 7) (c) but not serine 831 phosphorylation. d Intra-hippocampal overexpression of rAAV-hu-α-Syn did not affect the expression of the GluA2 subunit. Representative bands for each condition are reported. β-actin reported in 5d belong to the same blot reported in Supplementary Fig. 2a. e, f Field EPSPs input–output curves revealed a significant decrease in excitability in the HP-hu-α-Syn mice with respect to HP-GFP mice (two-way ANOVA: HP-hu-α-Syn n = 11, HP-GFP n = 11, F (11,220) = 5.090, Bonferroni’s post hoc test ***P < 0.001). g High-frequency stimulation (HFS)-induced LTP is reduced in hippocampal slices of HP-hu- α-Syn mice (green circles), compared to the HP-GFP group (gray circles) (two-way ANOVA: HP-hu-α-Syn n = 8, HP-GFP n = 11, F(23,391) = 2.690, Bonferroni’s post hoc test ***P < 0.001). Paired Student t test 2 min pre vs. 6 min post HFS: rAAV-GFP n = 11, t = 5.674, df = 10, ^###P < 0.001; rAAV-hu-α-Syn n = 8, t = 2.749, df = 7, ⁺P < 0.05; 2 min pre vs. 38 min post HFS: rAAV-GFP n = 11, t = 3.995, df = 10, ^##P < 0.01; rAAV-hu-α-Syn n = 8, t = 2.450, df = 7, ⁺P < 0.05. h Representative traces of evoked fEPSPs recorded before and 40 min after a high-frequency stimulation (HFS) protocol in HP-GFP CA1 (gray traces) and HP-α-Syn CA1 (green traces) animals. Data are presented as mean ± SEM. *P < 0.05 different from HP-GFP.