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Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: Possible anatomical substrates for viscerosensory modulation of exploratory behavior
Open accessAbstract
The presence of certain bacteria in the gastrointestinal tract influences behavior and brain function. For example, challenge with live Campylobacter jejuni (C. jejuni), a common food-born pathogen, reduces exploration of open arms of the plus maze, consistent with anxiety-like behavior, and activates brain regions associated with autonomic function, likely via a vagal pathway. As yet, however, little is known regarding the interface of immune sensory signals with brain substrates that mediate changes in behavioral states. To address this issue, we challenged mice with either C. jejuni or saline, and 7-8h later assessed anxiety-like behavior using the open holeboard, and used immunohistochemical detection of the protein c-Fos as an activation marker in the brain. C. jejuni treatment was associated with increased avoidance of the center regions of the holeboard, compared to saline-treated controls. Exposure to the holeboard induced activation in multiple brain regions previously implicated in anxiety-like behavior, including the lateral septum (LS), paraventricular (PVN) and dorsomedial hypothalamic nuclei (DMH), basolateral and central nuclei of the amygdala (BLA, CEA), bed nucleus of the stria terminalis (BST) and periaquiductal grey (PAG), compared to homecage controls. In C. jejuni-treated animals c-Fos induction also occurred in autonomic regions, as previously reported. The PVN, BLA, parts of the BST, medial prefrontal (mPFC) and anterior cingulate responded to both C. jejuni treatment and the holeboard, suggesting a role for these regions in the enhanced anxiety-like behavior observed. In saline-treated animals, anxiety-like behavior was predicted by activation in the CEA and BLA, whereas in C. jejuni-treated animals, c-Fos expression in the BST predicted the degree of anxiety-like behavior. These findings implicate the PVN, amygdala and BST as interfaces between gastrointestinal pathogenic challenge and brain regions that mediate behavioral responses to stress, and reinforce these nuclei as anatomical substrates by which viscerosensory stimuli can influence behavior.
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“There is also evidence for signaling between the GM and CNS, since microbes residing in the gut can activate stress circuits in the CNS through the vagus nerve and sensory neurons of the ENS (21, 49–54).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [50]
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Metadata
- Authors
- Goehler, L. E., Park, S. M., Opitz, N., Lyte, M., & Gaykema, R. P. A.
- Affiliations
- University of Virginia (US)
- University of Minnesota (US)
- Texas Tech University (US)
- Corresponding author
- Goehler, Lisa E.
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 22
- Issue
- 3
- Pages
- 354-366
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC2259293
- OpenAlex
- W2048617028
- Cited by
- 287
- References
- 52
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 25 · 2023: 16 · 2022: 26 · 2021: 27 · 2020: 23 · 2019: 21 · 2018: 24 · 2017: 19 · 2016: 22 · 2015: 20 · 2014: 13 · 2013: 8 · 2012: 9
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH068834, R01MH050431)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- Campylobacter jejuni, anxiety-like behavior, gut-brain axis, vagal pathway, c-fos, lateral septum, paraventricular nucleus, bed nucleus of the stria terminalis, amygdala, periaqueductal gray, exploratory behavior, stress response, food poisoning
- MeSH terms
- Amygdala, Animals, Anxiety, Brain, Campylobacter Infections, Exploratory Behavior, Immunohistochemistry, Male, Mice, Inbred Strains, Paraventricular Hypothalamic Nucleus, Septal Nuclei, Tissue Distribution, Campylobacter jejuni, Proto-Oncogene Proteins c-fos, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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