Fig. 4: Postsynaptic α-Syn rescues eCB plasticity in Syn-tKO mice by a cell-autonomous mechanism.
From: Postsynaptic synucleins mediate endocannabinoid signaling
a, Experimental approach. Top, AAV-mediated expression of α-Syn and GFP in dorsolateral striatum of Syn-tKO mice; bottom, Syn-tKO (GFP−) and α-Syn-expressing SPNs (GFP+) targeted for recordings. b,c, Top, Post hoc verification of α-Syn expression. b–f, Postsynaptic expression of full-length α-Syn in Syn-tKO cells is sufficient to rescue eCB-LTD (GFP–, pooled: n = 10 cells, 6 mice, 99. 04 ± 2.89%; GFP+, mSNCA: n = 11 cells, 6 mice, 72.71 ± 4.32%; P = 2.09 × 10−4). d, Postsynaptic expression of a C-terminus-truncated α-Syn (1–95) still rescued eCB-LTD in Syn-tKO mice (GFP+, 1–95: n = 9 cells, 5 mice, 73.47 ± 4.84%; P = 5.41 × 10−4). e, Summary of EPSC amplitudes. f, Summary of PPRs in full-length α-Syn-expressing cells (GFP+, mSNCA; baseline: 1.01 ± 0.03; post-DHPG: 1.11 ± 0.04; P = 2.0 × 10−3), C-terminus-truncated α-Syn-expressing cells (GFP+, 1–95; baseline: 1.07 ± 0.05; post-DHPG: 1.14 ± 0.06; P = 0.039) and GFP− cells (GFP−, pooled; baseline: 1.08 ± 0.03; post-DHPG: 1.09 ± 0.04; P = 1.0). g–i, Postsynaptic expression of full-length α-Syn rescues DSI in Syn-tKO SPNs (GFP− cells: n = 10 cells, 4 mice, pre-depol: 103.58 ± 4.01%, post-depol: 95.81 ± 4.88%, recovery: 90.66 ± 8.44%, P = 0.695, P = 0.770; GFP+ cells: n = 10 cells, 4 mice, pre-depol: 102.73 ± 3.19%, post-depol: 76.21 ± 4.29%, recovery: 98.32 ± 7.27%, P = 3.9 × 10−3, P = 0.027). i, Summary of DSI. Data are mean ± s.e.m. e,f,i, Box plots are depicted as mean (center), first/third quartiles (lower/upper box limits) and minima/maxima (bottom/top whiskers). Statistical significance was assessed by two-sided tests, including Wilcoxon signed tests (f,i) and ANOVA with multiple comparisons (e) (**P < 0.01; *P < 0.05; NS, not significant). depol, depolarization. Rec, recovery.
