Figure 2: Pathogenic mutant Tau reduces synaptic transmission and vesicle cycling/release during sustained high-frequency stimulation.
From: Tau association with synaptic vesicles causes presynaptic dysfunction
Drosophila larvae used in these assays express UAS-Tau (WT, R406W, V337M or P301L) under the D42-Gal4 motor neuron driver. (a,b) Electrophysiological recordings of synaptic transmission during 10 Hz stimulation for 10 min. Plot of evoked junction potential (EJP) amplitudes (a) and representative traces (b). Two-way ANOVA, ***P<0.0001, n=7 (Control, WT) or 9 (R406W, V337M, P301L) NMJs (animals). (c,d) FM1-43 dye loading with stimulation at 3 Hz (recycling vesicle pool) or 10 Hz (reserve vesicle pool) for 10 min. Representative images of FM1-43 dye loading (c) and plot of FM1-43 dye loading intensity (d). One-way ANOVA, **P=0.0028 (R406W), ***P=0.0001(V337M, P301L), n=14 (WT, R406W, V337M, P301L) or 20 (Control) NMJs (animals). Scale bar, 10 μm. (e–g) Synapto-pHluorin (SpH) responses to stimulation at 10 Hz with the presence of bafilomycin. Representative images of SpH responses (e) and plot of fluorescence change ΔF at ratio to maximal ΔF (NH4Cl dequenching) (f). Two-way ANOVA, ***P<0.0001, n=7 (WT, R406W, V337M, P301L) or 11 (Control) NMJs (animals). Plot of maximal ΔF (NH4Cl dequenching) calibrated to control levels (g). One-way ANOVA, ns, not significant. Scale bar, 20 μm. Data present mean±s.e.m.
