Extended Data Fig. 9: Absence of an effect on compulsive behaviour by normalization of release probability in persevering mice.
From: Stochastic synaptic plasticity underlying compulsion in a model of addiction
a, Average traces for EPSCs recorded immediately before and 30 min after the LTD protocol (10 Hz for 5 min) and grouped data. In slices from persevering mice, LTD is unmasked by bath application of mGluR5 PAM (CDPPB, 100 μM) and MK801 (NMDAR blocker, 10 μM) (two-sided t-test: t15 = 2.89, *P = 0.037, n = 8 and 9 cells, respectively). b, AMPAR/NMDAR ratio was left unchanged by in vivo stimulation of OFC–striatum terminals with 10 Hz in presence of MK801 and CDPPB (0.3 and 30 mg kg−1, respectively) in persevering mice (two-sided t-test: t53 = 1.86, P = 0.069 for control versus 10 Hz treated with MK801 and CDPPB (n = 29 and 26 cells, respectively)). c, PPR was normalized by in vivo stimulation of OFC–striatum terminals with 10 Hz in the presence of MK801 and CDPPB in persevering mice (two-sided t-test: t61 = 4.94, P < 0.0001 for control versus 10 Hz with MK801 and CDPPB (n = 38 and 25 cells, respectively)). The rectification index was different between controls and mice treated in vivo with the stimulation of OFC–striatum terminals at 10 Hz in the presence of MK801 and CDPPB (two-sided t-test: t53 = 2.25, *P = 0.029 for control versus 10 Hz with MK801 and CDPPB (n = 29 and 26 cells, respectively)). AMPAR/NMDAR ratio without pharmacological isolation was not different between controls and mice treated in vivo with the stimulation of OFC–striatum terminals at 10 Hz in the presence of MK801 and CDPPB (two-sided t-test: t54 = 1.57, P = 0.12 for control versus 10 Hz with MK801 and CDPPB (n = 30 and 26 cells, respectively)). d, Plots for delay between lever presses in punished sessions 12 h after 10 Hz, MK801 and CDPPB or 10 Hz with MK801and CDPPB (ANOVA followed by two-sided paired t-test: *P < 0.05 when comparing control/treatment delays during punished sessions). Perseverance is not modified by any treatment (two-sided t-test: t12 = 2.12, P = 0.056, n = 13 mice for control versus 10 Hz; t4 = 0.73, P = 0.51, n = 5 mice for control versus MK801 and CDPPB; t7 = 1.31, P = 0.231, n = 8 mice for control versus 10 Hz with MK801 and CDPPB). e, During additional punished sessions without renewal of the intervention, perseverance remained unchanged (n = 8 mice). Data are mean ± s.e.m. See Supplementary Table 1 for complete statistics.
