Fig. 1: Insular cortex activation as a key feature in (R)-ketamine-treated brain.

a Experimental timeline and schematic of the social isolation rearing and brain-wide IEG mapping after the forced swim test using Arc-dVenus mice. FST, forced swim test. b Immobility time of social isolation-reared Arc-dVenus mice treated with indicated drugs in the FST (for saline, 10 mg/kg (R)-ketamine, and 10 mg/kg (S)-ketamine; n = 5, in each group). Statistical analysis was performed using Levene’s test and one-way ANOVA, followed by Tukey’s multiple comparison test. Levene’s test: p = 0.223; one-way ANOVA: F(2, 12) = 8.129, p = 0.0059. *p < 0.05, **p < 0.01. (R)-ket, (R)-ketamine; (S)-ket, (S)-ketamine. c The box-whisker plot (center: median; box: 25–75th percentiles; whiskers: minimum to maximum) displays the z-score values for the number of dVenus-positive cells in each brain region. The abbreviations for the brain areas are provided in table S1. d The formula shows the transformation of classifier weights into corresponding activation patterns (left). The absolute values of the activation patterns of brain regions are plotted in the two indicated classifications. e Representative coronal images of the anterior insular cortex (aIC) of Arc-dVenus mice treated with indicated drugs (top). Scale bar, 500 µm. The anteroposterior distribution of dVenus-positive cells in the IC is shown in the bottom panel. mIC, the middle IC; pIC, the posterior IC. Statistical analysis was performed using Two-way ANOVA, followed by Tukey’s multiple comparison test: spatial distribution, F(9, 120) = 4.378, p < 0.0001; treatment, F(2, 120) = 14.12, p < 0.001; interaction, F(18, 120) = 1.191, p = 0.2791. **p < 0.01, ***p < 0.001, ****p < 0.0001. Data are presented as the mean ± standard error of the mean (s.e.m.).