386. DISRUPTION OF KINEMATIC PHENOTYPES INDUCED BY CANNABINOID AGONIST AND HARMALINE IN MARKER-BASED 3D MOTION CAPTURE OF FREELY MOVING MICE

Abstract Background We have developed a marker-based 3D motion capture system for high-precision quantification of locomotion in mice. This method allows measurement of fine 3D movement trajectories such as step kinematics during various behaviors with submillimeter accuracy. In our previous studies, we observed that a low dose of a synthetic agonist of cannabinoid CB1 and CB2 receptors, CP55,940 (0.3 mg/kg), causes a small reduction in general locomotion during open-field exploration but does not inhibit locomotion during vertical climbing. However, we observed that it induces significant changes in step kinematics, which were more pronounced during climbing. Aims & Objectives In the present study, we aimed to test whether the step kinematics of mice is affected during climbing and high-speed treadmill running under treatment with CP55,940 and tremor-inducing harmaline. Method We used adult male C57BL/6 mice in a within-subject, randomized design (n=6-10). We recorded voluntary climbing behavior on a spoked mesh wheel, as well as high-speed treadmill running in mice treated with vehicle (1:1:18 EtOH, Kolliphor, saline), a low dose of CP55,940 (0.3 mg/kg), or harmaline (20 mg/kg, i.p.) 30 min before recordings. Mice were implanted with permanent markers located on the hips, lumbar spine, shoulder blades, hindlimb knees, and ankles. A high-speed, high-resolution 3D motion capture system (Qualisys, Sweden) was used to track 3D trajectories and the velocity of markers during voluntary locomotory tasks: vertical climbing and running on a treadmill. On treadmill mice were running at speeds ranging from 1 m/min to 40 m/min, doubled with each trial until failure. Results During climbing CP55,940 did not reduce general locomotion but affected step kinematics decreasing step height and speed which is consistent with our previous observations. Harmaline, at 20 mg/kg induces strong whole-body tremor and was found to significantly inhibit locomotion during climbing and reduce the total number of steps. Harmaline also significantly inhibited the ability of mice to run on a treadmill. Interestingly CP55,940 also reduced the ability of mice to run on the treadmill despite having no effect on climbing. The maximum speed achieved on the treadmill was significantly decreased by harmaline and CP55,940 by >10 m/min on average. During treadmill running, ankle swings had significantly higher mean and maximum speeds than during vertical climbing or exploration tasks. Moreover, CP55,940 reduced the height of the ankle swing during treadmill running, similarly as it does during climbing. Discussion & Conclusions In conclusion, our results demonstrate the utility of marker-based 3D motion capture in accurate and precise measurement of high-speed fine kinematics such as running or tremor in mice. This innovation will help quantify motor impairments and disruption of kinematics in mouse models.