Understanding how the vagus nerve dynamically modulates higher brain function
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2024-04
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Melbourne Authors
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Anatomy and Neuroscience
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PhD thesis
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Open Access
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© 2024 Andrew Graham Butler
Abstract
Vagal nerve stimulation has emerged as a therapeutic intervention with a broad impact on various cognitive functions, including anxiety. This thesis focused on the role of a neural pathway linking viscerosensory vagal neurons to the locus coeruleus, via the nucleus of the solitary tract, in modulating anxiety-like behavior.
To investigate if vagal nerve stimulation modulates anxiety-like behavior, rats were instrumented to enable electrical stimulation of the vagus nerve and recording of diaphragm and cardiac activity. Vagal nerve stimulation was delivered prior to behavioral tests, including the elevated plus maze, open field test, novelty-suppressed feeding test, and real-time place preference assay, which assess anxiety-like behavior and affect. Low intensity vagal nerve stimulation decreased anxiety-like behavior, whereas higher intensity stimulation was aversive and increased anxiety-like behavior.
The central axonal projections of viscerosensory vagal neurons terminate in the nucleus of the solitary tract. To examine the ascending circuits involved in the effects of vagal nerve stimulation on anxiety-like behavior, the behavioral studies were repeated using optogenetic stimulation of nucleus of the solitary tract neurons, or just the axon terminals of these neurons in the locus coeruleus. Optogenetic stimulation of nucleus of the solitary tract neurons and their terminals in the locus coeruleus induced an anxiogenic phenotype in the novelty-suppressed feeding test, emphasizing the direct role of nucleus of the solitary tract to locus coeruleus projections in generating anxiety-like behavior. These outcomes also suggests the nucleus of the solitary tract and locus coeruleus may be involved in vagal mediated changes of anxiety-like behavior.
In conclusion, these findings highlight the bidirectional and stimulation dependent influence of vagal nerve stimulation on anxiety-like behavior. Furthermore, direct optical stimulation of a population of nucleus of the solitary tract neurons, or their projections to the locus coeruleus, increased anxiety-like behavior. I propose that this is an important pathway by which vagal nerve stimulation modulates anxiety. These observations provide valuable insights into the connections between organ function and motivated behavior, deepening our understanding of the nuanced relationship between vagal nerve stimulation and the neural mechanisms underlying anxiety regulation.
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Vagal Nerve Stimulation, Anxiety-like Behavior, Locus Coeruleus, Nucleus of the Solitary Tract, Viscerosensory Neurons, Optogenetics, Neural Pathways, Elevated Plus Maze, Open Field Test, Novelty-Suppressed Feeding Test, Real-Time Place Preference Assay, Interoception