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 3

Gastric vagotomy reduces anxiety-like behaviors in DSS-induced colitis mice.

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Gastric vagotomy reduces anxiety-like behaviors in DSS-induced colitis m...
(A) Schematic of the experimental timeline. (B) Schematic illustration of vagotomy methods. Bilateral gastric vagotomy (GV-Bi), bilateral subdiaphragmatic vagotomy (SDV-Bi), and vagotomy of left vagus (V-L). Blue represents anterior (right side) and red represents posterior (left side) of vagus. (C) Bar graph comparing the CCK-induced reduction of food intake (sham: n = 23; GV-Bi: n = 24; SDV-Bi: n = 23; GV-R: n = 13; SDV-R: n = 12; V-L: n = 13). (D–J) Black bars represent H2O groups, and red and orange bars represent DSS-treated groups (sham: n = 10; GV-Bi: n = 10; SDV-Bi: n = 10; sham-DSS: n = 13; GV-Bi-DSS: n = 14; GV-R-DSS: n = 13; SDV-Bi-DSS: n = 13; SDV-R-DSS: n = 12; V-L-DSS: n = 13). (D and E) Bar graphs comparing the effects of sham and vagotomy operations on the total distance traveled and the percentage of time spent in central zone in the OF test. (F and G) Bar graphs comparing the effects of sham and vagotomy operations on the duration in the light box and the number of entries into the light box in the LDB test. (H–J) Bar graphs comparing the effects of sham and vagotomy operations on the total distance traveled, the percentage of time spent in the open arms, and the percentage of time spent in the closed arms in the EPM test. Data represent the mean ± SEM. ##P < 0.01 and ###P < 0.001 by 2-tailed unpaired Student’s t test (D, E, F, and J) and Mann-Whitney U test (G–I); *P < 0.05, **P < 0.01, and ***P < 0.001 by Kruskal-wallis test with Dunn’s test (C) and 2-way ANOVA with Tukey’s multiple-comparison test (F–J).