Extended Data Fig. 6: Activity and manipulation of OFC–striatum projection during oDASS. | Nature

Extended Data Fig. 6: Activity and manipulation of OFC–striatum projection during oDASS.

From: Stochastic synaptic plasticity underlying compulsion in a model of addiction

Extended Data Fig. 6

a, Calcium signal (ΔF/F0, mean ± s.e.m.) around active press 1 and 2 of the FR3 schedule (numbers 1, 4, 7 and 2, 5, 8) during a baseline session for renouncing and persevering mice (green diamonds and pink bars indicate a significant deviation from baseline, n = 4 and 6 mice). b, Averaged calcium signal (ΔF/F0, mean ± s.e.m.) around active press 1 and 2 of the FR3 schedule (all but press number 8), around the active press number 8 (leading to the shock-associated cue) and around the lever press that terminates the non-shock FRs in punished sessions for renouncing and persevering mice (green diamonds and pink bars indicate a significant deviation from baseline, n = 4 and 6 mice). c, Example of trial activity map of the calcium signal (ΔF/F0, mean ± s.e.m.) around an unpredictable foot shock (500 ms, 0.25 mA, repeated in 10 times in one mouse). For each animal, 10 unpredictable foot shocks were delivered during a separate recording. Grouped data for the calcium signal (ΔF/F0, mean ± s.e.m.) around an unpredictable foot shock for renouncing and persevering mice (green diamonds and pink bars indicate a significant deviation from baseline, n = 4 and 6 mice). See Supplementary Table 1 for statistics. d, Scheme of a mouse brain infected with eArchT3.0–eYFP in the OFC and with ChR2–eYFP in the VTA (left). For persevering mice, OFC inhibition with eArchT3.0 between oDASS and the next FR initiation (or for a maximum of 90 s) delayed the next press of persevering mice (ANOVA followed by two-sided t-test: *P < 0.05 when comparing control versus eArchT3.0 delays during punished sessions, n = 13 mice). Perseverance changed (from 73% to 46%) as a consequence of eArchT3.0 stimulation (two-sided paired t-test: t12 = 9.13, *P < 0.0001, n = 13 mice for control versus eArchT3.0 before each FR initiation). e, For renouncing mice, OFC inhibition with eArchT3.0, after the punishment-predictive cue, between punished oDASS and the next FR initiation (or for a maximum of 90 s) or between each oDASS and the next FR initiation slightly delayed the next press (ANOVA followed two-sided paired t-test: *P < 0.05 when comparing control and eArchT3.0 delays during punished sessions). Perseverance was reduced as a consequence of eArchT3.0 stimulation between each oDASS and the next FR initiation (two-sided paired t-test: t7 = 2.62, *P = 0.034, n = 8 mice for control versus eArchT3.0 before each FR initiation). The oDASS rate during a baseline session was not significantly changed between punished oDASS and the next FR initiation (or for a maximum of 90 s) by inhibition with eArchT3.0. Data are mean ± s.e.m. See Supplementary Table 1 for complete statistics. d, Line drawing modified from Paxinos and Franklin44, copyright © 2007.

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