Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement
Author: Spencer Bowles1, Jordan Hickman2, Xiaoyu Peng1, W Ryan Williamson3, Rongchen Huang1, Kayden Washington1, Dane Donegan1, Cristin G Welle4
Affiliation:
1 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.
2 Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
3 IDEA Core, University of Colorado School of Medicine, Aurora, CO 80045, USA.
4 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.
Conference/Journal: Neuron
Date published: 2022 Jul 13
Other:
Special Notes: doi: 10.1016/j.neuron.2022.06.017. , Word Count: 171
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.
Keywords: basal forebrain; cholinergic; learning; motor cortex; motor learning; neuromodulation; outcome; plasticity; reinforcement; vagus nerve stimulation.
PMID: 35858623 DOI: 10.1016/j.neuron.2022.06.017
BACK
