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, ATTO550-labeled fibrillar a-Syn polymorphs for 15min, washed extensively and transferred to a fresh slice culture medium. Slices were fixed at different days and stored at 4°C until the end of experiment when immunohistochemistry for pS129-a-Syn was performed

, exogenous-a-Syn-ATTO550 (red, applied at 0.75µM, middle row) and overlaid channels (bottom row) following exposure of hippocampal organotypic slices to fibrillar a-Syn polymorphs Fibrils, Ribbons and Fibrils-91. The percentage of area occupied by pS129-a-Syn was plotted in E and total fluorescence of exogenous-a-Syn-ATTO550 was plotted in F. Box-plot shows median, inter-quartile range and 10-90% distribution. Mann-Whitney test performed to compare the difference from Day 4 for each polymorphs, Representative images (D) showing seeded endogenous pS129-a-Syn labeled with the antibody 81A (green, top row)

, H) pS129-a-Syn bundles (green) are stained by the autophagy marker p62 (red) in neurons cell bodies

I. , Hippocampal organotypic slices were exposed on day 0 to fibrillar a-Syn-ATTO550 polymorphs Fibrils, Ribbons and Fibrils-91 (0.75µM or 1.5µM) and immunolabeled with the anti-pS129-a-Syn antibody 81A on day 14 (F)

, Box-plot shows median, inter-quartile range and 10-90% distribution. Mann-Whitney test performed to compare the difference between 0.75µM and 1.5µM for each polymorphs

, A-J) Imunocytochemistry on DIV 21 of (A) a3-NKA (red) and Homer (green), (C) GluA2-AMPA receptors (red) and PSD95 (green), (E) GluN2B-NMDA receptors (red) and Homer (green) (G) GluA1-AMPA receptors (red) and PSD95 (green) and (I) mGluR5 receptors (red) and Homer (green), Figure 8. Differential re-distribution of synaptic a3-NKA/GluA2-AMPA/GluN2B-NMDA in primary neurons exposed to distinct a-Syn fibrillar polymorphs