GR presence in the VLO controls action flexibility
(A) Representative mCherry-expressing viral vector in the VLO of a YFP-expressing mouse. Cre infusion into “floxed” Nr3c1 mice reduced GR immunofluorescence in CaMKII+ neurons relative to infusion of a control viral vector in the opposite hemisphere. n = 7 mice, with comparison across hemispheres. Scale bars = 100μm.
(B) Cre infusion into “floxed” Nr3c1 mice also reduced GR protein levels in gross tissue punches. n = 4–6 mice/group.
(C) Timeline.
(D) Cocaine induced inflexible choice, as before, but GR silencing in the VLO prevented inflexible behavior. Interestingly, GR reduction induced inflexible behavior in cocaine-naïve mice. Pie charts represent the number of mice/group that preferentially responded at the “reinforced” aperture.
(E) Impulsive-like behavior was next assessed in the same mice using a delayed reinforcement task. Mice could preferentially respond for a large over small reinforcer.
(F) When a delay was introduced between responding for the large reinforcer and reinforcer delivery, mice switched preference to the small reinforcer. Drug-naïve mice with GR silencing generated lower response rates overall, though cocaine was without effect.
(G) Groups did not differ in sucrose consumption. n = 7–9 mice/group. ∗p < 0.05 following t-test when comparing 2 groups at a single time point and ANOVA when comparing >2 groups and/or multiple time points. Bars and connected dots represent means (±SEMs if indicated), and gray dots and lines represent individual mice.