Sex Differences in Head-fixed Running Behavior

ABSTRACT Sex differences in running behaviors between male and female mice occur naturally in the wild. Recent experiments using head restrained mice on a running wheel have exploited locomotion to provide insight in the neural underpinnings of a number of behaviors ranging from spatial navigation to decision making. However, it is largely unknown how males and females behave differently in this experimental paradigm. We found that in head-fixed mice that were initially exposed to a running wheel, all female mice ran forward naturally within the first two days, while almost all male mice scurried backward for up to 4 days. With daily exposure, male mice progressively learned to naturally run forward, with this transition occurring over the course of a 7-day period. Taken together, we have identified a sexually divergent behavior in head-fixed running that should be considered in experiments that use this experimental design. Furthermore, this sex-specific difference could serve as a new way to interrogate the neural underpinnings of a number of behaviors such as anxiety or fear.