Fig. 4: Chemogenetic inhibition of VTADA neurons promotes resilience to the CES-induced anxiety-like behavior. | Nature Communications

Fig. 4: Chemogenetic inhibition of VTADA neurons promotes resilience to the CES-induced anxiety-like behavior.

From: NAc-VTA circuit underlies emotional stress-induced anxiety-like behavior in the three-chamber vicarious social defeat stress mouse model

Fig. 4

a–f Verify the experimental validity of chemogenetic inhibition and in vivo electrophysiology recordings of VTADA neurons. a Schematic of virus infection and electrode implantation in VTA. b Experimental scheme of chemogenetic inhibition and in vivo electrophysiology recordings of VTADA neurons. c Raster plot of an hM4Di-mCherry mouse after normal saline (NS) or CNO injection. d Firing rate of VTADA neurons following NS or CNO administration (two-tailed paired t-test, P = 0.0038), n = 16 neurons from 3 mice. e Representative image of VTA injection sites. Scale bar, 100 μm. f The quantitative analysis of Venn diagram shows the co-expression level of mCherry with TH in VTA (3 sections per mouse from 5 mice). g–q Bilateral chemogenetic inhibition of VTADA neurons and behavioral tests (n = 10 mice for each group). g Schematic of bilateral virus infection. h Experimental scheme of CES modeling and chemogenetic inhibition of VTADA neurons and behavioral tests. i–l Results of OFT. i Representative exploration traces of OFT. j Percentage of time spent in the central area of OFT (two-way ANOVA, group: P = 0.0002, treatment: P = 0.0001, interaction: P = 7.80 × 10−5; post hoc Tukey’s test, hM4Di(NS vs. CNO): P = 2.46 × 10−6, CNO(mCherry vs. hM4Di): P = 2.90 × 10−6). k Percentage of distance traveled in the central area of OFT (two-way ANOVA, group: P = 0.0250, treatment: P = 0.0033, interaction: P = 0.0075; post hoc Tukey’s test, hM4Di(NS vs. CNO): P = 0.0009, CNO(mCherry vs. hM4Di): P = 0.0043). l Total distance traveled in the OFT (two-way ANOVA, group: P = 0.3714, treatment: P = 0.9985, interaction: P = 0.3757; post hoc Tukey’s test, hM4Di(NS vs. CNO): P = 0.9207, CNO(mCherry vs. hM4Di): P = 0.5848). m–o Results of EPM. m Representative exploration traces in EPM. n Percentage of time spent in the open arms of EPM (two-way ANOVA, group: P = 0.0127, treatment: P = 0.0052, interaction: P = 0.0070; post hoc Tukey’s test, hM4Di(NS vs. CNO): P = 0.0011, CNO(mCherry vs. hM4Di): P = 0.0023). o Number of open-arm entries in the EPM (two-way ANOVA, group: P = 0.2143, treatment: P = 0.0356, interaction: P = 0.0046; post hoc Tukey’s test, hM4Di(NS vs. CNO): P = 0.0040, CNO(mCherry vs. hM4Di): P = 0.0221). p, q Results of SIT. p Representative traces in SIT. q Statistics of time spent in the social interaction zone of SIT (two-way ANOVA, group: P = 0.6860, treatment: P = 0.8187, interaction: P = 0.7186; post hoc Tukey’s test, hM4Di(NS vs. CNO): P = 0.9997, CNO(mCherry vs. hM4Di): P = 0.9999). The red and blue dots in the OFT, EPM, and SIT locomotion traces reflect the start and end points of the mouse, respectively. All data are shown as mean ± SEM. ns not significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.

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