Fig. 3

Inhibition of mPFC Drd1 expressing cells blocks the antidepressant effect of ketamine. a Representative AAV-ARCH viral expression in ventral mPFC. b Action potentials induced by current injection in voltage clamp are potently inhibited by ARCH activation. c Current clamp recordings demonstrate hyperpolarization associated with light application. d Voltage clamp recordings demonstrate outward current during light application. e FST immobility time 24 h after photoinhibition and ketamine (Factorial ANOVA interaction p = 0.11). f Time to feed in the NSF test 72 h after photoinhibition and ketamine administration (Mantel–Cox (log rank) overall p < 0.01, WT-veh vs. WT-ket p < 0.05). g Representative AAV-hM4Di expression. h FST immobility time 24 h after hM4Di inhibition and ketamine (Factorial ANOVA interaction p < 0.01, post-hoc t-test p < 0.001). i Time to feed in the NSF 72 h after hM4Di inhibition and ketamine (Mantel–Cox (log rank) overall p < 0.05, WT-veh vs. WT-ket p < 0.01). e, f n = 5 males, 3 females per group; h, i n = 5 males, 5 females per WT group, n = 4 males, 5 females Cre ket, n = 5 males, 4 females Cre veh; *p < 0.05, **p < 0.01, ***p < 0.001. Error bars represent mean ± SEM, scale bar 100 µM. Male—closed data points, female—open data points