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

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 7

Chemogenetic inhibition of LC-NE projections to the BLA reduces anxiety-like behaviors in DSS-induced colitis mice.

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Chemogenetic inhibition of LC-NE projections to the BLA reduces anxiety-...
(A) Left: schematic of the experimental timeline. Right: AAVDJ-hSyn-DIO-hM4Di-mCherry was injected into the LC of DSS-treated DBH-Cre mice, and CNO was microinfused into the BLA. (B) Representative images showing mCherry expression in the LC (left, red) and cannula implantation site in the BLA (right; bottom). Scale bar: 100 μm. The mCherry-labeled LC neurons were immunopositive for NET (green) indicated by arrowheads. Augmented figures (right) show mCherry-labeled neurons in rectangle area. Scale bar: 20 μm. (C and D) Bar graphs comparing the effects of saline and CNO injection on the total distance traveled (n = 10 in each group) (C) and the percentage of time spent in central zone (n = 10 in each group) (D) in the OF test. (E and F) Bar graphs comparing the effects of saline and CNO injection on the duration in the light box (n = 10 in each group) (E) and the number of entries into the light box (n = 10 in each group) (F) in the LDB test. (G–I) Bar graphs comparing the effects of saline and CNO injection on the total distance traveled (n = 10 in each group) (G), the percentage of time spent in the open arms (n = 10 in each group) (H), and the percentage of time spent in the closed arms (n = 10 in each group) (I) in the EPM test. Data represent the mean ± SEM. *P < 0.05 and **P < 0.01 by 2-tailed unpaired Student’s t test.