Gut Vagal Afferents Differentially Modulate Innate Anxiety and Learned Fear
Open accessAbstract
Vagal afferents are an important neuronal component of the gut–brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior.
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Gut vagal afferents influence anxiety and learned fear.
“Recently, it has been shown that gut vagal afferents also influence anxiety and learned fear (Klarer et al. 2014).”
From Motion sickness: more than nausea and vomiting (2014) · cites this paper as Klarer et al. 2014
Subdiaphragmatic vagal deafferentation highlights the involvement of vagal afferents in anxiety-like and fear-related behavior.
“In addition, subdiaphragmatic vagal deafferentation (Vazquez et al., 2016) a method that eliminates abdominal vagal afferents, but keeps most efferents intact (Norgren and Smith, 1994) highlights the involvement of vagal afferents in anxiety-like (elevated plus maze, open-field test, food neophobia) and fear-related behavior (auditory-cued fear conditioning) (Klarer et al.,”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Klarer et al., 2014
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A Brain-Melanocortin-Vagus Axis Mediates Adipose Tissue Expansion Independently of Energy Intake
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- Authors
- Klarer, M., Arnold, M., Günther, L., Winter, C., Langhans, W., & Meyer, U.
- Affiliations
- ETH Zurich (CH)
- University Hospital Carl Gustav Carus (DE)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-05-21
- Volume
- 34
- Issue
- 21
- Pages
- 7067-7076
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6608191
- OpenAlex
- W2028119064
- Cited by
- 159
- References
- 56
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 18 · 2023: 11 · 2022: 14 · 2021: 12 · 2020: 17 · 2019: 16 · 2018: 12 · 2017: 12 · 2016: 16 · 2015: 7 · 2014: 3
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Repository for Publications and Research Data (ETH Zurich) (publishedVersion, cc-by-nc-sa)
- ETH Zürich Research Collection
- Funders
- European Commission (259679)
- Eidgenössische Technische Hochschule Zürich (ETH-25_13-2, 25_13-2)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- vagal afferents, gut-brain axis, learned fear, fear extinction, norepinephrine, GABA, limbic system, hypothalamic-pituitary-adrenal axis, emotional behavior, food neophobia
- MeSH terms
- Animals, Anxiety, Conditioning, Classical, Eating, Exploratory Behavior, Extinction, Psychological, Fear, Functional Laterality, Male, Sincalide, Vagus Nerve, Rats, Sprague-Dawley, Neurotransmitter Agents, Maze Learning, Gastrointestinal Tract, Rats
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