Fig. 1: eCB-dependent LTD is abolished in Syn-tKO mice.
From: Postsynaptic synucleins mediate endocannabinoid signaling
a, Experimental configuration (bottom, one representative differential interference contrast (DIC) image of ~700 whole-cell recordings included in this study). b, Top, representative traces of evoked corticostriatal EPSCs across a range of stimulation intensities. Bottom, input–output curves in WT and Syn-tKO mice (WT: n = 12 cells, 6 mice; Syn-tKO: n = 13 cells, 6 mice; P = 0.888). c, Representative traces of responses to repeated stimulation across a range of stimulation frequencies. d,e, No difference in use-dependent synaptic properties in Syn-tKO mice, as measured by short-term depression dynamics (d; WT: n = 14 cells, 4 mice; Syn-tKO: n = 11 cells, 3 mice; 5 Hz: P = 0.304; 50 Hz: P = 0.651; 100 Hz: P = 0.691) and steady-state amplitudes (e; P = 0.756) in response to repeated stimulation across a range of frequencies. f, Schematic of eCB-LTD experiments. Top, whole-cell recordings from SPNs during induction of eCB-LTD; bottom, eCB-LTD induction with DHPG (50 µM) and depolarization (−50 mV). g–j, DHPG-induced eCB-LTD in WT mice is fully blocked by the CB1R antagonist AM251 (10 µM) (WT: n = 11 cells, 4 mice, 69.95 ± 1.70%; WT + AM251: n = 8 cells, 5 mice, 96.89 ± 3.42%; P = 6.375 × 10−4); top, representative traces. h, eCB-LTD is abolished in Syn-tKO mice (Syn-tKO: n = 11 cells, 4 mice, 97.76 ± 3.49%; P = 2.106 × 10−4); top, representative trace. i, Summary of EPSC amplitudes. j, Summary of PPRs (WT baseline: 1.18 ± 0.04; post-DHPG: 1.39 ± 0.06; P = 0.001; Syn-tKO baseline: 1.17 ± 0.05; post-DHPG: 1.19 ± 0.05; P = 0.831; WT + AM251 baseline: 1.26 ± 0.06; post-DHPG: 1.27 ± 0.06; P = 0.641). Data are mean ± s.e.m. i,j, 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 two-way repeated-measures ANOVA with multiple comparisons (b,d,e), ANOVA with multiple comparisons (i) and Wilcoxon signed tests (j) (***P < 0.001; **P < 0.01; NS, not significant).
