PMC

a, Sample traces recorded from VTA-mPFC neurons in VTA slices. b, Firing rates of VTA-mPFC neurons from control, resilient, and susceptible mice (F₂,_.38 = 15.07, p=0.0005; post-hoc test, * p<0.005; n=11–15). c, Social interaction data obtained by optical stimulation of VTA-mPFC neurons in control, tonic, and phasic groups (F₂,₃₉ = 1.29, p=0.29; n=11–17). d, Sucrose preference data measured over a 12-hr period after the social interaction test (F₂,₃₃ = 0.19, p=0.82; n=10–16). e, Social interaction data obtained during optical inhibition of VTA-mPFC neurons (t₂₉ = 2.5, * p<0.05; two tailed t-test, n=12–19). f, Sucrose preference measured over a 12-hr period after the social interaction test (t₂₉=0.38, p>0.05, n=12–19). All bar graphs depict ± s.e.m.

a, Sample traces recorded from VTA-NAc neurons in VTA slices. b, Firing rates of VTA-NAc neurons from control, resilient, and susceptible mice (F₂,₈₉ = 15.77, p<0.001; post-hoc test, * p<0.001; n=12–52). c, Social interaction data obtained during optical stimulation of VTA-NAc neurons in control, tonic, and phasic groups. (F₂,₂₀ = 4.43, p<0.05; post-hoc test: * p<0.05; n=5–10). d, Sucrose preference data measured over a 12-hr period after the social interaction test. (F₂,₁₈ = 4.80, p<0.05; post-hoc test, * p<0.05; n=5–9). e, Social interaction during optical inhibition of VTA-NAc neurons in previously susceptible mice (No target: t₁₅ = 4.2, * p<0.001; two tailed t-test, n=8-9; Target: t₁₅ = 2.6, * p<0.05; two tailed t-test, n=8–9). f, Sucrose preference measured over a 12-hr period after the social interaction test (t₁₄ = 2.3, * p<0.05; two tailed t-test, n=8–9). All bar graphs depict ± s.e.m.

Confocal image showing co-expression of AAV-DIO-ChR2 in TH+ DA cells from TH-Cre mice. b, Quantification shows that ChR2-expressing TH+ cells are 62±4% of total TH+ neurons in the VTA and there was no expression of ChR2 in TH- neurons (n=2–3 sections from n=4 animals). c, Optical stimulation protocols for mimicking tonic (0.5 Hz) or phasic (20 Hz) firing. Note that for both stimulating protocols, five spikes are induced over each ten second period. d1, Experimental timeline. d2, Detailed schematic of the subthreshold paradigm showing laser stimulation during social defeat. e, Social interaction data in control, tonic, and phasic groups. (F₂,₃₀ = 4.70, p<0.05; post-hoc test: * p<0.05; n=7–14). f. Sucrose preference measured over a 12-hr period after the social interaction test (F₂,₂₂ = 5.22, p<0.05; post-hoc test, * p<0.05; n=7–10). All bar graphs depict ± s.e.m.

a, Social interaction data in control, tonic, and phasic groups (F₂,₂₂ = 4.00, p<0.05; post-hoc test: * p<0.05; n=7–11). b, Sucrose preference measured over a 12-hr period after the social interaction test (F₂,₂₅ = 3.47, p<0.05; post-hoc test: * denotes p<0.05; n=8–11). c, Social interaction data measured on day 17 (t₁₅ = 2.72, * denotes p<0.05; two tailed t-test, n=11–18). d, Sucrose preference measured over a 12-hr period after the social interaction test (t₁₇ = 2.34, * p<0.05; two tailed t-test, n=6–12). e, Sample traces: showing in vitro spontaneous activity of VTA DA neurons from TH-Cre mice that underwent tonic and phasic stimulation during the social interaction test 24 hr after subthreshold social defeat (see for the experimental timeline). Bar graph: Comparison of spontaneous firing in VTA DA neurons from EYFP-control, tonic, and phasic-stimulated mice (F_2,50 = 3.19, p<0.05; post-hoc test, * p<0.05; n=17–19). f, Significantly less current was required to evoke a single spike in phasic stimulated mice compared to EYFP control mice (t₂₁ = 1.8, * p<0.05; one tailed t-test, n=12–16). g, VTA DA cells from phasic stimulated mice display overall increased cell excitability to incremental steps in current injections (50, 100, 150 and 200pA) compared with EYFP control and tonic stimulated mice (F_2,140 = 16.13, p<0.001; post-hoc test, * p<0.05 ** p<0.005; n=5–17). All bar graphs depict ± s.e.m.