Chemogenetic induction of associative learning requires GIRK channel activation. A, Currents evoked by CNO (10 μm) in BA pyramidal neurons from CaMKIICre(+)/hM4Di (Girk1+/+; red) and CaMKIICre(+):Girk1fl/fl/hM4Di (Girk1–/–; gray) mice. Currents were reversed by bath application of 0.3 mm Ba2+. B, Summary of CNO-induced currents in hM4Di-positive BA pyramidal neurons from CaMKIICre(+)/hM4Di (Girk1+/+; red) and CaMKIICre(+):Girk1fl/
fl/hM4Di (Girk1–/–; gray) mice (t(11)=3.9, **p = 0.003; n = 6–7/group). C, CNO-induced change in rheobase (Δrheobase) in hM4Di-positive BA pyramidal neurons from CaMKIICre(+)/hM4Di (Girk1+/+; red) and CaMKIICre(+):Girk1fl/fl/hM4Di (Girk1–/–; gray) mice (t(9)=3.6, **p = 0.006; n = 6–7/group). D, Saline (gray) or CNO (2 mg/kg, i.p.; black) was administered to CaMKIICre(+):Girk1fl/fl/hM4Di mice, 30 min before training in the 3 CS/0 US protocol. Freezing during training is plotted on the left. Yellow bars represent the CS presentations. There was no effect of genotype (F(1,84)=0.3, p = 0.58). Freezing during context (t(14)=0.6, p = 0.57) and cue (t(13)=0.9, p = 0.38) recall tests is plotted on the right (n = 8 mice/group). Bars represent the mean ± SEM, with dots next to each bar denoting the individual data points. Sex effects were not analyzed for this study.