Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement

Vagus nerve stimulation (VNS) is a neuromodulation therapy for a broad and expanding set of neurologic con-ditions. 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 un-derstand 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.

Automated summary

Vagus nerve stimulation is a neuromodulation therapy that influences specific neural circuits through widespread brain activation, enhancing behavioral learning. By investigating neuronal activity in mice during a reach task, researchers found that VNS modulates neurons in the motor cortex through cholinergic signaling, accelerating motor refinement.