Closed-loop automated reaching apparatus (CLARA) for interrogating complex motor behaviors

Abstract

Abstract Objective. Closed-loop neuromodulation technology is a rapidly expanding category of therapeutics for a broad range of indications. Development of these innovative neurological devices requires high-throughput systems for closed-loop stimulation of model organisms, while monitoring physiological signals and complex, naturalistic behaviors. To address this need, we developed CLARA, a closed-loop automated reaching apparatus. Approach. Using breakthroughs in computer vision, CLARA integrates fully-automated, markerless kinematic tracking of multiple features to classify animal behavior and precisely deliver neural stimulation based on behavioral outcomes. CLARA is compatible with advanced neurophysiological tools, enabling the testing of neurostimulation devices and identification of novel neurological biomarkers. Results. The CLARA system tracks unconstrained skilled reach behavior in 3D at 150 Hz without physical markers. The system fully automates trial initiation and pellet delivery and is capable of accurately delivering stimulation in response to trial outcome with short latency. Kinematic data from the CLARA system provided novel insights into the dynamics of reach consistency over the course of learning, suggesting that learning selectively improves reach failures but does not alter the kinematics of successful reaches. Additionally, using the closed-loop capabilities of CLARA, we demonstrate that vagus nerve stimulation (VNS) improves skilled reach performance and increases reach trajectory consistency in healthy animals. Significance. The CLARA system is the first mouse behavior apparatus that uses markerless pose tracking to provide real-time closed-loop stimulation in response to the outcome of an unconstrained motor task. Additionally, we demonstrate that the CLARA system was essential for our investigating the role of closed-loop VNS stimulation on motor performance in healthy animals. This approach has high translational relevance for developing neurostimulation technology based on complex human behavior.