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 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,...

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Vydáno v:	Neuron (Cambridge, Mass.) Ročník 110; číslo 17; s. 2867
Hlavní autoři:	Bowles, Spencer, Hickman, Jordan, Peng, Xiaoyu, Williamson, W Ryan, Huang, Rongchen, Washington, Kayden, Donegan, Dane, Welle, Cristin G
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 07.09.2022
Témata:	Animals Brain Cholinergic Agents - pharmacology Mice Nervous System Diseases - therapy Neuronal Plasticity - physiology Vagus Nerve Stimulation - methods neuromodulation motor cortex motor learning basal forebrain cholinergic plasticity learning vagus nerve stimulation reinforcement outcome
ISSN:	1097-4199, 1097-4199
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Abstract	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.
AbstractList	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.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. 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.
Author	Welle, Cristin G Hickman, Jordan Williamson, W Ryan Washington, Kayden Huang, Rongchen Donegan, Dane Bowles, Spencer Peng, Xiaoyu
Author_xml	– sequence: 1 givenname: Spencer surname: Bowles fullname: Bowles, Spencer organization: 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 – sequence: 2 givenname: Jordan surname: Hickman fullname: Hickman, Jordan organization: Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045, USA – sequence: 3 givenname: Xiaoyu surname: Peng fullname: Peng, Xiaoyu organization: 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 – sequence: 4 givenname: W Ryan surname: Williamson fullname: Williamson, W Ryan organization: IDEA Core, University of Colorado School of Medicine, Aurora, CO 80045, USA – sequence: 5 givenname: Rongchen surname: Huang fullname: Huang, Rongchen organization: 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 – sequence: 6 givenname: Kayden surname: Washington fullname: Washington, Kayden organization: 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 – sequence: 7 givenname: Dane surname: Donegan fullname: Donegan, Dane organization: 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 – sequence: 8 givenname: Cristin G surname: Welle fullname: Welle, Cristin G email: cristin.welle@cuanschutz.edu organization: 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
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SubjectTerms	Animals Brain Cholinergic Agents - pharmacology Mice Nervous System Diseases - therapy Neuronal Plasticity - physiology Vagus Nerve Stimulation - methods
Title	Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement
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