Vagus nerve stimulation (VNS) is a neuromodulation therapy for a broad and expanding set of neurologic conditions. However, the mechanism through which VNS influences central nervous system circuitry is not well described, limiting therapeutic optimization. VNS leads to widespread brain activation, but the effects on behavior are remarkably specific, indicating plasticity unique to behaviorally engaged neural circuits. To understand how VNS can lead to specific circuit modulation, we leveraged genetic tools including optogenetics and in vivo calcium imaging in mice learning a skilled reach task. We find that VNS enhances skilled motor learning in healthy animals via a cholinergic reinforcement mechanism, producing a rapid consolidation of an expert reach trajectory. In primary motor cortex (M1), VNS drives precise temporal modulation of neurons that respond to behavioral outcome. This suggests that VNS may accelerate motor refinement in M1 via cholinergic signaling, opening new avenues for optimizing VNS to target specific disease-relevant circuitry.

迷走神经刺激 (VNS) 是一种神经调节疗法，适用于广泛且不断扩大的神经系统疾病。然而，VNS 影响中枢神经系统回路的机制尚未得到很好的描述，限制了治疗的优化。VNS 会导致广泛的大脑激活，但对行为的影响非常具体，这表明行为参与的神经回路具有独特的可塑性。为了了解 VNS 如何导致特定的电路调制，我们利用了遗传工具，包括光遗传学和体内学习熟练完成任务的小鼠的钙成像。我们发现 VNS 通过胆碱能强化机制增强健康动物的熟练运动学习，从而快速巩固专家的到达轨迹。在初级运动皮层 (M1) 中，VNS 驱动对行为结果做出反应的神经元的精确时间调制。这表明 VNS 可能通过胆碱能信号加速 M1 的运动精细化，为优化 VNS 以靶向特定疾病相关电路开辟了新途径。