Vagal nerve stimulation dynamically alters anxiety-like behavior in rats
Background: Electrical vagal nerve stimulation (VNS), at currents designed to target sensory, interoceptive neurons, decreases anxiety-like behavior. Objective/Hypothesis: We hypothesized that different VNS current intensities would differentially alter anxiety-like behavior through the activation o...
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Elsevier
2025-03-01
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author | A.G. Butler J.K. Bassi A.A. Connelly M.R. Melo A.M. Allen S.J. McDougall |
author_facet | A.G. Butler J.K. Bassi A.A. Connelly M.R. Melo A.M. Allen S.J. McDougall |
author_sort | A.G. Butler |
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description | Background: Electrical vagal nerve stimulation (VNS), at currents designed to target sensory, interoceptive neurons, decreases anxiety-like behavior. Objective/Hypothesis: We hypothesized that different VNS current intensities would differentially alter anxiety-like behavior through the activation of distinct brainstem circuits. Methods: Electrodes were implanted to stimulate the left vagus nerve and to record diaphragm muscle and electrocardiogram activity. The VNS current required to elicit the A-fiber-mediated Hering-Breuer Reflex (HBR) was determined for each animal. Based on this threshold, animals received either sham stimulation or VNS at 1.5 (mid-intensity VNS) or 3 (higher-intensity VNS) times the threshold for HBR activation. Anxiety-like behavior was assessed using the elevated plus maze, open field test, and novelty-suppressed feeding test. Additionally, a place preference assay determined whether VNS is rewarding or aversive. Finally, a c-Fos assay was performed to evaluate VNS-driven neuronal activation within the brainstem. Results: Mid-intensity VNS reduced anxiety-like behavior in the elevated plus maze and open field test. Higher-intensity VNS was aversive during the place preference assay, confounding anxiety measures. Both intensities increased overall c-Fos expression in neurons within the nucleus of the solitary tract, but mid-intensity VNS specifically increased c-Fos expression in noradrenergic neurons within the nucleus of the solitary tract while decreasing it in the locus coeruleus. In contrast, higher-intensity VNS had no effect on c-Fos expression in noradrenergic neurons of either the nucleus of the solitary tract or locus coeruleus. Conclusion: Delivery of VNS induced reproducible, current intensity-dependent, effects on anxiety-like and aversive behavior in rats. |
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id | doaj-art-d51d0e4108d54857acbadefc78ce5187 |
institution | Kabale University |
issn | 1935-861X |
language | English |
publishDate | 2025-03-01 |
publisher | Elsevier |
record_format | Article |
series | Brain Stimulation |
spelling | doaj-art-d51d0e4108d54857acbadefc78ce51872025-02-10T04:34:18ZengElsevierBrain Stimulation1935-861X2025-03-01182158170Vagal nerve stimulation dynamically alters anxiety-like behavior in ratsA.G. Butler0J.K. Bassi1A.A. Connelly2M.R. Melo3A.M. Allen4S.J. McDougall5Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, AustraliaDepartment of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, AustraliaDepartment of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, AustraliaDepartment of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, AustraliaFlorey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, Australia; Corresponding author. Department of Anatomy and Physiology University of Melbourne, Parkville, VIC, 3010, AustraliaFlorey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Corresponding author. Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3010, Australia.Background: Electrical vagal nerve stimulation (VNS), at currents designed to target sensory, interoceptive neurons, decreases anxiety-like behavior. Objective/Hypothesis: We hypothesized that different VNS current intensities would differentially alter anxiety-like behavior through the activation of distinct brainstem circuits. Methods: Electrodes were implanted to stimulate the left vagus nerve and to record diaphragm muscle and electrocardiogram activity. The VNS current required to elicit the A-fiber-mediated Hering-Breuer Reflex (HBR) was determined for each animal. Based on this threshold, animals received either sham stimulation or VNS at 1.5 (mid-intensity VNS) or 3 (higher-intensity VNS) times the threshold for HBR activation. Anxiety-like behavior was assessed using the elevated plus maze, open field test, and novelty-suppressed feeding test. Additionally, a place preference assay determined whether VNS is rewarding or aversive. Finally, a c-Fos assay was performed to evaluate VNS-driven neuronal activation within the brainstem. Results: Mid-intensity VNS reduced anxiety-like behavior in the elevated plus maze and open field test. Higher-intensity VNS was aversive during the place preference assay, confounding anxiety measures. Both intensities increased overall c-Fos expression in neurons within the nucleus of the solitary tract, but mid-intensity VNS specifically increased c-Fos expression in noradrenergic neurons within the nucleus of the solitary tract while decreasing it in the locus coeruleus. In contrast, higher-intensity VNS had no effect on c-Fos expression in noradrenergic neurons of either the nucleus of the solitary tract or locus coeruleus. Conclusion: Delivery of VNS induced reproducible, current intensity-dependent, effects on anxiety-like and aversive behavior in rats.http://www.sciencedirect.com/science/article/pii/S1935861X25000208NeuromodulationAfferentAutonomicAnxiolyticAnxiogenicState dependent |
spellingShingle | A.G. Butler J.K. Bassi A.A. Connelly M.R. Melo A.M. Allen S.J. McDougall Vagal nerve stimulation dynamically alters anxiety-like behavior in rats Brain Stimulation Neuromodulation Afferent Autonomic Anxiolytic Anxiogenic State dependent |
title | Vagal nerve stimulation dynamically alters anxiety-like behavior in rats |
title_full | Vagal nerve stimulation dynamically alters anxiety-like behavior in rats |
title_fullStr | Vagal nerve stimulation dynamically alters anxiety-like behavior in rats |
title_full_unstemmed | Vagal nerve stimulation dynamically alters anxiety-like behavior in rats |
title_short | Vagal nerve stimulation dynamically alters anxiety-like behavior in rats |
title_sort | vagal nerve stimulation dynamically alters anxiety like behavior in rats |
topic | Neuromodulation Afferent Autonomic Anxiolytic Anxiogenic State dependent |
url | http://www.sciencedirect.com/science/article/pii/S1935861X25000208 |
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