Heterozygosity for Prkar2a rescued the running phenotype. Voluntary running activity was graphed in bins of 30 minutes over a 2-week period for (A) female (n = 11–24/genotype) and (B) male (n = 8–12/genotype) RIIα-KO, RIIα+/–, and WT mice and (C) the total number of wheel turns during the 2-week period, analyzed by 1-way ANOVA with multiple comparisons (Bonferroni’s post hoc test). (D) Representative staining for c-Fos or c-Jun (red) (merged with DAPI) in WT and RIIα-KO mice either permitted to run as already acclimated for 2 weeks prior or blocked from running at the outset of the dark cycle (1800 hours). (E) The same images (4D) are shown with only c-Fos or c-Jun (red) and particle density of c-Fos and c-Jun was analyzed with ImageJ software (NIH); unpaired 2-way t tests, n = 5–17 sections from a total 3–5 mice per IEG/genotype (3 males, 7 females). Particle density is defined as the number of counted particles divided by the area ratio of the MHb, with the latter being the area of the MHb over the total image area. All data represent mean ± SEM; scale bars represent 100 μm; **P < 0.01, ***P < 0.001, ****P < 0.0001.