Extended Data Fig. 5: ENS neurotransmission is disrupted by αSyn pathology and restored by GBA1 gene transfer.

a, Quantification of average peak percent change in fluorescence and area under the curve after photostimulation pulse for jRGECO1a⁺-only or jRGECO1a⁺/ChR2⁺ duodenal neurons before and after inoculation (all ****p < 0.0001). b, Quantification of average peak percent change in fluorescence and area under the curve after photostimulation pulse for jRGECO1a⁺-only or jRGECO1a⁺/ChR2⁺ duodenal neurons before and after systemic delivery of AAV-PHP.S::ihSyn:GBA1 (Peak ΔF/F jRGECO1a⁺ 0 dpvi WT vs. ASO ****p < 0.0001, 7 dpvi WT vs. ASO ****p < 0.0001; Peak ΔF/F jRGECO1a⁺/ChR2⁺ 0 dpvi WT vs. ASO ****p < 0.0001, 7 dpvi WT vs. ASO ***p = 0.0006; AUC jRGECO1a⁺ 0 dpvi WT vs. ASO ****p < 0.0001, 7 dpvi WT vs. ASO **p = 0.0031; AUC jRGECO1a⁺/ChR2⁺ 0 dpi WT vs. ASO *p = 0.0398). Data depicted are mean ± s.e.m. P values were determined by two-way ANOVA. The following n values represents number of independent animals used for statistical evaluation: e5a, 0 dpi = 3, PFF 7 dpi = 4, PFF 60 dpi = 3, monomer 7 dpi = 3, monomer 60 dpi = 3; e5b, all conditions = 3.

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