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Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice
Chin-Hao Chen, Tsung-Chih Tsai, Yi-Jen Wu, Kuei-Sen Hsu
Chin-Hao Chen, Tsung-Chih Tsai, Yi-Jen Wu, Kuei-Sen Hsu
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Research Article Neuroscience

Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice

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Abstract

Inflammatory bowel disease (IBD) is a relapsing-remitting disorder characterized by chronic inflammation of the gastrointestinal (GI) tract. Anxiety symptoms are commonly observed in patients with IBD, but the mechanistic link between IBD and anxiety remains elusive. Here, we sought to characterize gut-to-brain signaling and brain circuitry responsible for the pathological expression of anxiety-like behaviors in male dextran sulfate sodium–induced (DSS-induced) experimental colitis mice. We found that DSS-treated mice displayed increased anxiety-like behaviors, which were prevented by bilateral GI vagal afferent ablation. The locus coeruleus (LC) is a relay center connecting the nucleus tractus solitarius to the basolateral amygdala (BLA) in controlling anxiety-like behaviors. Chemogenetic silencing of noradrenergic LC projections to the BLA reduced anxiety-like behaviors in DSS-treated mice. This work expands our understanding of the neural mechanisms by which IBD leads to comorbid anxiety and emphasizes a critical role of gastric vagal afferent signaling in gut-to-brain regulation of emotional states.

Authors

Chin-Hao Chen, Tsung-Chih Tsai, Yi-Jen Wu, Kuei-Sen Hsu

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Figure 2

DSS-induced colitis causes anxiety-like behaviors.

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DSS-induced colitis causes anxiety-like behaviors.
 (A) Representative m...
(A) Representative movement traces of H2O- and DSS-treated mice in the OF test. (B and C) Bar graphs comparing the effects of H2O and DSS treatment on the total distance traveled and the percentage of time spent in central zone (H2O: n = 13; DSS: n = 12) in the OF test. (D and E) Bar graphs comparing the effects of H2O and DSS treatment on the duration in the light box and the number of entries into the light box (H2O: n = 13; DSS: n = 12) in the LDB test. (F) Representative movement traces of H2O- and DSS-treated mice in the EPM test. (G–I) Bar graphs comparing the effects of H2O and DSS treatment on the total distance traveled, the percentage of time spent in the open arms, and the percentage of time spent in the closed arms (H2O: n = 13; DSS: n = 12) in the EPM test. Data represent the mean ± SEM. *P < 0.05 and *** P < 0.001 by Mann-Whitney U test (B, G, and H) and 2-tailed unpaired Student’s t test (C, D, E, and I).

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