Fig. 3: eCB release is impaired in Syn-tKO mice.
From: Postsynaptic synucleins mediate endocannabinoid signaling
a, Schematic of WIN-LTD experiments. b–d, Normal WIN-LTD in WT and Syn-tKO mice (WT: n = 9/7, 39.91 ± 3.18%; Syn-tKO: n = 8/3, 42.46 ± 4.36%; P = 0.673). e, PPRs in WT mice (baseline: 1.09 ± 0.07; post-WIN: 1.36 ± 0.12; P = 3.9 × 10−3) and Syn-tKO mice (baseline: 0.99 ± 0.04; post-WIN: 1.33 ± 0.07; P = 7.8 × 10−3). f, Schematic of eCB-loading experiments. g–j, eCB-loading causes LTD in WT cells, blocked by AM251 (AEA WT: n = 9/3, 72.40 ± 3.10%; AEA WT + AM251: n = 7/5, 99.13 ± 2.63%; P = 1.08 × 10−5; 2-AG WT: n = 8/5, 74.92 ± 4.66%). h, eCB loading fails to induce LTD in Syn-tKO cells (AEA Syn-tKO: n = 9/3, 98.16 ± 3.05; P = 7.08 × 10−6; 2-AG Syn-tKO: n = 7/4, 101.22 ± 2.46%; P = 6.21 × 10−4). eCB loading increases PPRs in WT cells (AEA baseline: 1.02 ± 0.04; end: 1.19 ± 0.05; P = 3.9 × 10−3; 2-AG baseline: 1.26 ± 0.08; end: 1.38 ± 0.09; P = 7.8 × 10−3), not Syn-tKO cells (AEA baseline: 1.00 ± 0.04; end: 1.00 ± 0.05; P = 0.82; 2-AG baseline: 1.44 ± 0.07; end: 1.45 ± 0.06; P = 0.81). k, Top, GRABeCB2.0 activation; bottom, representative image (1/32) of a GRABeCB2.0-expressing slice. l, Stimulation increases GRABeCB2.0 signal in WT condition; top, representative images. m–o, Stimulation-evoked GRABeCB2.0 transients in Syn-tKO slices are reduced (WT: n = 16/5, 0.31 ± 0.07 ΔF/F0; Syn-tKO: n = 16/4, 0.05 ± 0.02 ΔF/F0; P = 8.52 × 10−4). l,m,o, No differences between WT and Syn-tKO slices with AEA (WT: 0.61 ± 0.09 ΔF/F0; Syn-tKO: 0.37 ± 0.07 ΔF/F0; P = 0.073) or AM251 (WT: −0.05 ± 0.04 ΔF/F0; Syn-tKO: 0.02 ± 0.03 ΔF/F0; P = 0.086). Data are mean ± s.e.m. n = cells or slices per mouse. d,e,i,j,n,o, Box plots are depicted as mean, first/third quartiles and minima/maxima. Significance was assessed by two-sided tests: Mann–Whitney tests (d,j,n,o), Wilcoxon signed tests (e) and ANOVA with multiple comparisons (i) (****P < 0.0001; ***P < 0.001; **P < 0.01; NS, not significant).
