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.

客观的。闭环神经调节技术是一个快速扩展的治疗类别，适用于广泛的适应症。这些创新神经设备的开发需要高通量系统来对模型生物体进行闭环刺激，同时监测生理信号和复杂的自然行为。为了满足这一需求，我们开发了 CLARA，一种闭环自动到达装置。方法。利用计算机视觉领域的突破，CLARA 集成了多种特征的全自动、无标记运动学跟踪，对动物行为进行分类，并根据行为结果精确地提供神经刺激。CLARA 与先进的神经生理学工具兼容，可以测试神经刺激设备并识别新型神经生物标志物。结果。CLARA 系统以 150 Hz 的 3D 频率跟踪不受限制的熟练触及行为，无需物理标记。该系统完全自动化试验启动和颗粒输送，并且能够以短延迟准确地输送刺激以响应试验结果。来自 CLARA 系统的运动学数据为学习过程中伸展一致性的动态提供了新颖的见解，表明学习有选择地改善伸展失败，但不会改变成功伸展的运动学。此外，利用 CLARA 的闭环功能，我们证明迷走神经刺激 (VNS) 可以提高健康动物的熟练伸展性能并提高伸展轨迹的一致性。意义。CLARA 系统是第一个使用无标记姿势跟踪来提供实时闭环刺激以响应无约束运动任务结果的小鼠行为装置。此外，我们证明 CLARA 系统对于我们研究闭环 VNS 刺激对健康动物运动表现的作用至关重要。这种方法对于开发基于复杂人类行为的神经刺激技术具有高度的转化相关性。