# Vagus nerve stimulation drives plasticity through inhibitory interneurons

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $561,405

## Abstract

Project Summary
Closed-loop VNS was recently approved by the FDA to restore upper limb mobility for patients with stroke.
Moreover, preclinical and early clinical studies suggest that closed-loop VNS improves recovery from conditions
such as spinal cord injury, traumatic brain injury, post-traumatic stress disorder and addiction. Despite the wide-
ranging etiology of these conditions, the therapeutic model is similar; VNS is paired with a relevant rehabilitation
protocol. The precise timing of stimulation is a key element to drive specific circuit plasticity and functional
recovery. Yet, VNS activates widespread brain networks, raising the question of how closed-loop VNS can lead
to circuit-specific alterations in plasticity and functional recovery.
 The goal of this proposal is to identify the mechanism by which closed-loop VNS drives circuit-specific
plasticity during motor learning and stroke recovery. Our lab has shown, for the first time, that VNS elicits phasic
cholinergic signaling from the basal forebrain (BF) and modulates inhibitory interneurons in motor cortex.
Cholinergic signaling from BF is recognized to play a critical role in learning and plasticity and recovery from
injury. The influence of cholinergic signaling on cortical plasticity is mediated through inhibitory interneurons,
which gate synaptic plasticity within cortex.
 We hypothesize that closed-loop VNS drives recovery from stroke through cholinergic modulation of
inhibitory interneurons to produce circuit-specific plasticity. The objectives of this proposal will be 1) to determine
if closed-loop VNS drives synaptic plasticity on active circuits via cholinergic signaling; 2) to determine the
influence of cholinergic signaling on inhibitory interneuron gating of synaptic plasticity and; 3) to explore the role
of cholinergic activity and inhibitory interneuron gating of plasticity during stroke recovery. This data will provide
a detailed mechanism by which closed-loop VNS can drive plasticity in the healthy and injured nervous system.

## Key facts

- **NIH application ID:** 10901273
- **Project number:** 1R01NS137560-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Cristin G Welle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $561,405
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901273

## Citation

> US National Institutes of Health, RePORTER application 10901273, Vagus nerve stimulation drives plasticity through inhibitory interneurons (1R01NS137560-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10901273. Licensed CC0.

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