Motor vs. cognitive elements of apparent “hyperlocomotion”: A conceptual and experimental clarification

Locomotion, described as “the combination of forward progression carrying the animal from one location to the next, and stopping/scanning involving investigation of particular locations” (1), is an innate behavior heavily used as a defining phenotypic trait in animal studies related to motor disorders, including Parkinson’s disease. Hence, it is important to design and analyze behavioral experiments in ways that allow the distinction between motor vs. cognitive contributions to movement patterns. In a recent study on the effect of selectively reducing glutamate transmission in a subtype 2 Vesicular glutamate transporter (Vglut2)-expressing subpopulation of the subthalamic nucleus [Vglut2f/f;Pitx2-Cre conditional knockout (cKO) mice], Schweizer et al. use an elegant multidisciplinary methodology that combines behavioral, anatomical, electrophysiological, and molecular experiments (2). Notwithstanding the power of their molecular approach, we have strong reservations about Schweizer et al.’s interpretation of the behavioral assessment. The authors measure spontaneous locomotion over 60 min in an “open field setting” on 2 consecutive days; they find increased total activity in cKO mice and conclude that the selective genetic manipulation is sufficient to cause hyperlocomotion while largely sparing cognitive and affective behavior. Here we argue that their data do not unequivocally establish the former and only incompletely examine the latter.