Ventral tegmental area dopaminergic neurons contribute to hindlimb control during obstacle-avoidance locomotion in mice

Introduction Dopamine neurons in the midbrain contribute to motor, cognitive and memory functions, and their degeneration has been implicated in gait instability and increased fall risk during obstacle-avoidance behavior. However, the specific contribution of ventral tegmental area (VTA) dopaminergic neurons to visually guided locomotion remains poorly understood. Methods We examined obstacle-avoidance locomotion in mice that received bilateral injections of either 6-hydroxydopamine (6-OHDA) or saline into the VTA. High-speed motion-capture analysis was used to evaluate obstacle-contact frequency, limb kinematics, and forelimb–hindlimb coordination. Results Compared with the saline-injected control group, the 6-OHDA lesion group exhibited a higher frequency of contacts by the leading hindlimb, including both stomps and grazes. Stomping was associated with impaired adjustment of stride length and landing position, whereas grazing occurrence was unrelated to takeoff position. In addition, the leading hindlimb in the lesion group initiated toe elevation earlier during obstacle negotiation, a change not observed during overground locomotion. Furthermore, the lesion group exhibited greater forelimb–hindlimb distance immediately before obstacle crossing, suggesting impaired interlimb coordination. Discussion Collectively, these findings suggest that VTA dopamine neurons contribute to memory-guided control of the leading hindlimb during obstacle negotiation. These results may provide insight into mechanisms underlying altered obstacle negotiation in patients with Parkinson’s disease.