Patterns of brain activity associated with variation in voluntary wheel-running behavior

Rodents spontaneously run on wheels, but what underlies variation within and between species is unknown. This study used Fos immunoreactivity to compare brain activity in mice selectively bred for high wheel running (S) versus control (C) mice. Mice ran for 6 days, but on Day 7, half the mice were prevented from running. A strong positive correlation was found between running distance and Fos in the dentate gyrus of C runners that was lost in S runners. In mice prevented from running, Fos was higher in S than in C in the lateral hypothalamus, medial frontal cortex, and striatum. Results implicate specific brain regions in motivation to run and others in control of the intensity of the locomotor behavior itself.