Fig. 6: Defeat alters frontocortical and hippocampal neuronal activity in defeated animals during social investigation.

a Confocal image of mouse anterior cingulate cortex stained for the immediate early gene (IEG) cFos (green) 45 min after the day 2 avoidance test, 20x, scale bar = 100 µm. b Quantification of cFos+ cells in extrahippocampal brain regions active during the investigation of a CD1 mouse 24 h after aSD. The number of cFos+ neurons in the mPFC, in total, and the prelimbic (PL) subregion were significantly lower in Cre+ mice that had been defeated when compared to No Defeat control animals (mPFC: No Defeat: 116.4 ± 13.3 cells vs. Defeat Cre + : 76.3 ± 10.2, N = 5 and 7 mice, respectively, one-way ANOVA F = 3.44 p = 0.059, unpaired t-test p = 0.035:: PL: No Defeat: 90.3 ± 5.6 cells vs. Defeat Cre + : 64.0 ± 8.7 cells, N = 5 and 7 mice, respectively, one-way ANOVA F = 2.50 p = 0.115, unpaired t-test p = 0.044). Similarly, cFos+ cells were significantly lower in number in the ACC of Cre+ defeated mice compared to No Defeat controls (No Defeat: 269.6 ± 63.0 cells vs. Defeat Cre + : 102.1 ± 48.8 cells, N = 11 and 11 mice, respectively, one-way ANOVA F = 2.44 p = 0.95, unpaired t-test p = 0.048). aSD had no effect on cFos expression in either the dorsal lateral septum (dLS: No Defeat: 12.5 ± 1.3 cFos+ cells vs. Defeat Cre-: 10.4 ± 1.3 cells vs. Defeat Cre + : 13.7 ± 2.2 cells, N = 11, 12 and 11 mice, respectively) or ventral lateral septum (vLS: No Defeat: 91.7 ± 9.0 cells vs. Defeat Cre-: 107.7 ± 14.1 cells vs. Defeat Cre + : 109.3 ± 8.8 cells, N = 11, 12 and 11 mice) during investigation of a novel CD1 mouse. c. Confocal image of mouse cHPC stained for cFOS (green) following the day 2 avoidance test, 20x, scale bar = 500 µm. d cFOS+ neurons counts were significantly lower in cCA3, cCA1 total, ventral cCA1 and the cHPC in total in defeated mice when compared to No Defeat controls (cCA3: one-way ANOVA F = 3.32 p = 0.052, No Defeat: 20.4 ± 2.6 cells vs. Defeat Cre + : 12.9 ± 1.1 cells, N = 9 and 10 mice, unpaired t-test p = 0.014 :: cCA1: one-way ANOVA F = 4.14 p = 0.027, No Defeat: 67.7 ± 9.0 cells vs. Defeat Cre-: 43.1 ± 5.2 cells vs. Defeat Cre + : 43.4 ± 6.2 cells, N = 9, 10 and 10 mice; No Defeat vs. Defeat Cre-, unpaired t-test p = 0.026; No Defeat vs. Defeat Cre + , unpaired t-test p = 0.037:: cCA1v: one-way ANOVA F = 5.59 p = 0.0095, No Defeat: 38.3 ± 5.0 cells vs. Defeat Cre-: 23.9 ± 3.1 cells vs. Defeat Cre + : 20.1 ± 3.8 cells, N = 9, 10 and 10 mice; No Defeat vs. Defeat Cre-, unpaired t-test p = 0.024; No Defeat vs. Defeat Cre + , unpaired t-test p = 0.001) :: cHPC total: one-way ANOVA F = 3.95 p = 0.032, No Defeat: 106.0 ± 12.0 cells vs. Defeat Cre-: 74.8 ± 8.5 cells vs. Defeat Cre + : 71.8 ± 7.5 cells, N = 9, 10 and 10 mice; No Defeat vs. Defeat Cre-, unpaired t-test p = 0.046; No Defeat vs. Defeat Cre + , unpaired t-test p = 0.023. e Confocal image of mouse rostral hippocampus stained for cFOS (green) following the day 2 avoidance test, 20x, scale bar = 100 µm. f Although the number of cFos+ cells trended lower in the rCA3 subregion and for total positive cells, this reduction is only significant when comparing control mice with Cre- defeated animals (rCA3: one-way ANOVA F = 2.60 p = 0.090, No Defeat: 50.0 ± 7.4 cells vs. Defeat Cre-: 33.7 ± 5.3 cells vs. Defeat Cre + : 31.7 ± 5.7 cells, N = 11, 13 and 11 mice :: rCA1: one-way ANOVA F = 4.16 p = 0.025, No Defeat: 42.4 ± 10.7 cells vs. Defeat Cre-: 15.0 ± 3.9 cells vs. Defeat Cre + : 19.4 ± 6.1 cells, N = 11, 13 and 11 mice; No Defeat vs. Defeat Cre-, unpaired t-test p = 0.018 :: rHPC total: one-way ANOVA F = 1.82 p = 0.18, No Defeat: 113.0 ± 20.6 cells vs. Defeat Cre-: 92.0 ± 13.5 cells vs. Defeat Cre + : 94.6 ± 16.8 cells, N = 11, 13 and 11 mice, respectively). *p < 0.05.