Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement.
Spencer Bowles, Jordan Hickman, Xiaoyu Peng, W Ryan Williamson, Rongchen Huang, Kayden Washington, Dane Donegan, Cristin G Welle
Author Information
Spencer Bowles: Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Jordan Hickman: Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Xiaoyu Peng: Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045, USA.
W Ryan Williamson: IDEA Core, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Rongchen Huang: Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Kayden Washington: Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Dane Donegan: Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Cristin G Welle: Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: cristin.welle@cuanschutz.edu.
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.
