FIGURE 7.
Lrrc4c–/– brain regions with distinct changes in neuronal activity upon EPM stimulation. (A–K) Brain regions at examined brain sections (S) that show strong EPM-induced increases in c-fos levels (indicated by the number of c-fos-positive cells) in WT mice, but moderate or no increases in Lrrc4c–/– mice (3–4 months; male). Results for the colored regions within each brain diagram are indicated in the corresponding color-coded bar graphs. Blue and red shades in the brain diagrams indicate the statistical significance of both main factors or their interaction. Orange shades indicate statistical significance of only the genotype factor. n = 16 slices from 4 mice (WT), n = 16 (4) (KO), ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ns, not significant, two-way ANOVA (genotype × stimulus) with Holm-Sidak multiple comparison test [(A) interaction, F(1,63) = 2.14, p = 0.149; genotype, F(1,63) = 12.79, p = 0.0007; stimulus, F(1,63) = 6.51, p = 0.0133; WT (E vs. C), p = 0.0062, KO (E vs. C), p = 0.4444, Control (WT vs. KO), p = 0.1401, EPM (WT vs. KO), p = 0.0007; (B) two-way ANOVA; interaction, F(1,63) = 1.99, p = 0.1631; genotype, F(1,63) = 18.11, p < 0.001; stimulus, F(1,63) = 5.01, p = 0.0289; WT (E vs. C), p = 0.0123, KO (E vs. C), p = 0.5608, Control (WT vs. KO), p = 0.0489, EPM (WT vs. KO), p = 0.0002; (C) two-way ANOVA; interaction, F(1,63) = 22.42, p < 0.001; genotype, F(1,63) = 29.45, p < 0.001; stimulus, F(1,63) = 85.22, p < 0.001; WT (E vs. C), p < 0.001, KO (E vs. C), p = 0.0023, Control (WT vs. KO), p = 0.6266, EPM (WT vs. KO), p < 0.001; (D) two-way ANOVA; interaction, F(1,63) = 4.82, p = 0.0321; genotype, F(1,63) = 50.97, p < 0.001; stimulus, F(1,63) = 6.04, p = 0.0169; WT (E vs. C), p = 0.0017, KO (E vs. C), p = 0.8527, Control (WT vs. KO), p = 0.0009, EPM (WT vs. KO), p < 0.001; (E) interaction, F(1,60) = 0.9534, p = 0.3328; genotype, F(1,60) = 30.7815, p < 0.001; stimulus, F(1,60) = 1.637, p = 0.2057; (F) interaction, F(1,63) = 13.27, p = 0.0006; genotype, F(1,63) = 19.17, p < 0.001; stimulus, F(1,63) = 66.44, p < 0.001; WT (E vs. C), p < 0.001, KO (E vs. C), p = 0.0023, Control (WT vs. KO), p = 0.6046, EPM (WT vs. KO), p < 0.001; (G) interaction, F(1,63) = 7.67, p = 0.0074; genotype, F(1,63) = 12.79, p < 0.001; stimulus, F(1,63) = 6.51, p = 0.0059; WT (E vs. C), p = 0.0002, KO (E vs. C), p = 0.4444, Control (WT vs. KO), p = 0.1259, EPM (WT vs. KO), p < 0.001; (H) interaction, F(1,63) = 4.02, p = 0.0494; genotype, F(1,63) = 9.03, p = 0.0039; stimulus, F(1,63) = 79.76, p < 0.001; WT (E vs. C), p < 0.001, KO (E vs. C), p < 0.001, Control (WT vs. KO), p = 0.4828, EPM (WT vs. KO), p = 0.0008; (I) interaction, F(1,63) = 4.53, p = 0.0373; genotype, F(1,63) = 3.64, p = 0.0612; stimulus, F(1,63) = 167.04, p < 0.001; WT (E vs. C), p < 0.001, KO (E vs. C), p < 0.001, Control (WT vs. KO), p = 0.876, EPM (WT vs. KO), p = 0.0059; (J) interaction, F(1,63) = 5.32, p = 0.0245; genotype, F(1,63) = 9.4, p = 0.0032; stimulus, F(1,63) = 127.03, p < 0.001; WT (E vs. C), p = 0.0018, KO (E vs. C), p = 0.3961, Control (WT vs. KO), p = 0.0422, EPM (WT vs. KO), p < 0.001; (K) interaction, F(1,58) = 5.2833, p = 0.0252; genotype, F(1,58) = 53.793, p < 0.001; stimulus, F(1,58) = 13.8661, p = 0.0004; WT (E vs. C), p = 0.0001, KO (E vs. C), p = 0.0009, Control (WT vs. KO), p = 0.3255, EPM (WT vs. KO), p = 0.0002]. (L–O) Brain regions that show strong EPM-induced decreases (not increases) in c-fos levels in both WT and Lrrc4c–/– mice (3–4 months; male). Note that because baseline c-fos levels are lower in Lrrc4c–/– mice, final c-fos levels after EPM stimulation are also lower in Lrrc4c–/– mice. n = 16 (4) (WT), n = 16 (4) (KO), ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, two-way ANOVA (genotype × stimulus) Holm-Sidak multiple comparison test [(L) interaction, F(1,63) = 5.78, p = 0.0193; genotype, F(1,63) = 47.13, p < 0.001; stimulus, F(1,63) = 32.18, p < 0.001; WT (E vs. C), p < 0.001, KO (E vs. C), p = 0.0243, Control (WT vs. KO), p < 0.001, EPM (WT vs. KO), p = 0.0025; (M) interaction, F(1,63) = 0.01, p = 0.9247; genotype, F(1,63) = 49.42, p < 0.001; stimulus, F(1,63) = 32.32, p < 0.001; WT (E vs. C), p = 0.0003, KO (E vs. C), p = 0.0002, Control (WT vs. KO), p = 0.0001, EPM (WT vs. KO), p = 0.0001; (N) interaction, F(1,63) = 0.02, p = 0.9018; genotype, F(1,63) = 16.02, p = 0.0002; stimulus, F(1,63) = 22.47, p < 0.001; WT (E vs. C), p = 0.0018, KO (E vs. C), p = 0.0011, Control (WT vs. KO), p = 0.008, EPM (WT vs. KO), p = 0.005; (O) interaction, F(1,63) = 0.4, p = 0.5273; genotype, F(1,63) = 17.49, p < 0.001; stimulus, F(1,63) = 14.92, p = 0.0003; WT (E vs. C), p = 0.0023, KO (E vs. C), p = 0.0261, Control (WT vs. KO), p = 0.0012, EPM (WT vs. KO), p = 0.0149].