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Vagal nerve stimulation dynamically alters anxiety-like behavior in rats
A G Butler1, J K Bassi2, A A Connelly2
1Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, Australia.
Brain Stimulation
|February 1, 2025
Summary
Vagal nerve stimulation (VNS) intensity-dependently alters anxiety-like behavior in rats. Mid-intensity VNS reduces anxiety, while higher intensities can be aversive and impact brainstem circuits.
Area of Science:
- Neuroscience
- Behavioral Science
- Medical Devices
Background:
- Electrical vagal nerve stimulation (VNS) targeting sensory neurons is known to reduce anxiety-like behavior.
- The precise mechanisms and intensity-dependent effects of VNS on neural circuits remain incompletely understood.
Purpose of the Study:
- To investigate how different VNS current intensities differentially alter anxiety-like behavior.
- To explore the underlying brainstem circuit activation patterns associated with varying VNS intensities.
Main Methods:
- Vagus nerve electrodes were implanted in rats to deliver VNS at 1.5x (mid-intensity) or 3x (higher-intensity) the threshold for the Hering-Breuer Reflex (HBR).
- Anxiety-like behaviors were assessed using elevated plus maze, open field, and novelty-suppressed feeding tests.
- Place preference and c-Fos assays evaluated VNS rewarding/aversive properties and VNS-driven neuronal activation in the brainstem.
Main Results:
- Mid-intensity VNS significantly reduced anxiety-like behavior in behavioral tests.
- Higher-intensity VNS demonstrated aversive properties and confounded anxiety assessments.
- Both VNS intensities increased c-Fos in the nucleus of the solitary tract; mid-intensity VNS uniquely modulated noradrenergic neurons in the nucleus of the solitary tract and locus coeruleus.
Conclusions:
- VNS delivery produces reproducible, current intensity-dependent effects on anxiety-like and aversive behaviors in rats.
- These findings highlight the critical role of VNS intensity in modulating specific brainstem pathways and behavioral outcomes.
