Fig. 4: Inhibition of VTA glutamatergic neurons promotes susceptibility to STA. | Nature Communications

Fig. 4: Inhibition of VTA glutamatergic neurons promotes susceptibility to STA.

From: Midbrain glutamatergic circuit mechanism of resilience to socially transferred allodynia in male mice

Fig. 4

a Experimental timeline. b, c Representative immunofluorescent images and quantitative data of c-Fos protein expression in mCherry-positive VTA glutamatergic neurons after saline or CNO treatment in Vglut2-IRES-Cre mice (adapted from The Mouse Brain in Stereotaxic Coordinates by Paxinos and Franklin). Scale bar: 600 and 150 µm; n = 6, 6 slices from 3 mice/group, P = 1.1 × 10−6. d PWTs for different subgroups of BY mice across three repeats of social transfer of allodynia paradigm with or without chemogenetic inhibition of VTA glutamatergic neurons, subgroups of BY mice were identified according to the behavioral outcome after their first exposure to social contact with CFA partners (n = 10, 17 and 19 mice). Control versus BY-R, PBL = 0.7498, PT1 = 0.6023, PT2 = 0.0018, PT3 = 0.5510. e Percentages of BY-S and BY-R mice across the three repeats of social transfer of allodynia paradigm. Test 1 versus Test 2, P = 0.0017; Test 1 versus Test 3, P > 0.9999; Test 2 versus Test 3, P = 0.0042. f Experimental timeline and chemogenetic inhibition of VTA glutamatergic neurons in BY-R mice following the 1 h of social contact. g PWTs over different time points before and after CNO injection in BY-R mice (n = 9, 13, 9 and 8 mice). BY-R + saline versus BY-R + CNO, PBL = 0.5942, P30min = 0.0017, P2h = 0.2435, P6h = 0.9935. h Experimental timeline and chemogenetic inhibition of VTA glutamatergic neurons in BY mice during a 15 min of sub-threshold social contact. i PWTs after chemogenetic inhibition of VTA glutamatergic neurons during the sub-threshold social contact (n = 9, 8 and 8 mice). Control versus BY + CNO, PBL = 0.9082, P30min = 2.2 × 10−5, P2h = 0.0324, P6h = 0.0647, P12h = 0.0284, P24h = 0.9961. The data are presented as the mean ± s.e.m. *P < 0.05, **P < 0.01, ****P < 0.0001, ns no significance. Data analyzed by (c) unpaired two-sided t-test; (d, g, i) two-way RM ANOVA with Tukey’s multiple comparisons test and (e) two-sided Fisher’s exact test. Statistical details are presented in Supplementary Table 5. Source data are provided as a Source Data file.

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