Fig. 4: Cooperative role of TCF/LEF and REST in the recovery from depression.

a, b SI-rate and TF-activities for each mouse expressing both TCF/LEF- and REST-reporters. 3D plot (a) and the Pearson correlation analysis (b). Control, 14; defeat, 18 mice. c Single-cell level TF-activity in PFC neurons. The t-SNE plot illustrates the clustered cells after social defeat (top) and the distribution of TF-activity for TCF/LEF (middle) and REST (bottom). See Fig. S6 for details. Each TF-activity was compared to the control average within the clusters, with cells showing high-activity and low-activity indicated in dark/light colors. d, e Results of bulk RNA-seq analysis in the anterior cortex of defeated mice treated with lithium or sertraline (n  =  3 mice each). TPM (d) and changes between the two drug treatments (15,881 genes) (e). The dotted lines indicate p-value of 0.05 and log₂-fold changes of ± 1. f Effects of multiple drug treatments. Experimental scheme (top) and changes in SI-rates. Mean ± sem; two-way ANOVA; number of mice in each cohort — sertraline and lithium + sertraline; day 1: 14, 12; day 3: 15, 12; day 8: 15, 12; day 15: 15, 12. g The proportion of socially defeated mice not exhibiting depressive symptoms following drug treatments, compared between days 1–3 (top) and days 8–15 (bottom) post-stress exposure. The p-values were calculated based on a binomial test compared to vehicle-treated controls and corrected using the Holm method. Summarized data include those shown in Figs. 2d, 3j, 4f and Supplementary Fig. S1b.