Towards Developing a Closed-Loop System to Optogenetically Perturb Cerebellar Purkinje Cells and Assess Effects on Locomotion in Freely-Moving Mice, Mina Musthafa, UG '22, (3965173)

The cerebellum has long been identified as a brain region involved in motor control and balance. Previously, it had been challenging to study cerebellar control of motor coordination in a context that did not involve constant user input, but recent advances in computer vision have helped to address this problem. Better understanding the role of the cerebellum in coordinating locomotion is important because such research could have implications for neuro-prosthetics in patients with movement disorders. Given that optogenetic techniques--the use of light to activate cells--are commonly used for probing cerebellar neurons, voluntary locomotion in control mice in an open field was compared with locomotion affected by optogenetic perturbation of Purkinje cells (important for coordinating locomotion) in experimental mice so as to assess if Purkinje cell stimulation significantly alters locomotion. The experimental set-up involved using Social LEAP Estimates Animal Pose (SLEAP), a pose estimation tool, in conjunction with DeepLabStream, an analytical framework that allows for real-time monitoring. Overall, perturbing cerebellar purkinje cells results in locomotion that can no longer be characterized as an oscillator (coordinated movement of limbs). The use of DeepLabStream with SLEAP proves promising towards the development of a closed-loop system that would enable a more efficient way of probing the perturbation of Purkinje cells via optogenetic stimulation. While neuro-prosthetics involving cerebellar control may still be a future aim, research investigating the control of locomotion through perturbing cerebellar Purkinje cells is an important step towards such a goal.