Developing a Behavioral Assay to Quantify and Probe Motor Behaviors

Locomotion is a critical aspect of an organism’s fitness and is broadly conserved across phyla. In vertebrates, the ability to traverse distances through coordinated limb movement remains a quintessential process, one that is often compromised in human-conditions of motor impairment such as stroke, Parkinson’s disease, and various ataxias. To understand the biological basis of the observed human locomotor deficits research groups have largely relied on murine models of motor-disease and behavioral assays that test gross gait patterns or motor learning (e.g., Rotarod). Yet, given the recent developments in marker-less limb tracking and novel behavioral preparations of locomotor activity, the possibility to characterize locomotion and gait a single digit/limb resolution in murine models of health and disease is increasingly possible. To achieve this goal, locomotion characterized at single-digit resolution, we adopted two mouse locomotion preparations from previous works in the field and introduced multi-camera imaging paired with marker-less position tracking (DeepLabCut) to track the position of individual digits during each task. Initial preparations of both behavioral assays (KineMouse Wheel and motorized-disk) were found to be stress inducing, which contributed to abnormal gait/locomotion. To resolve this confound, we introduced motor enrichment in the home cages, which was key in establishing normal gait. We developed a final protocol based on the motorized-disk task, in which we were successfully able to replicate previous findings. With the behavioral preparation replicated, we integrated a novel imaging platform that integrates digit position from multiple perspectives. The resulting data was analyzed through DeepLabCut to understand the fine motor behaviors of head-fixed mice while running. With this foundation in place, we are poised to make comparisons with diseased-model mice. This knowledge will aid in taking steps towards developing neural prosthetics, treatments for neurodegenerative diseases, and, improve everyday life activities for those who suffer from motor impairments. Bachelor of Scienc