Brain regulation of gastric dysfunction induced by stress.

Psychological and physical stressors have been implicated in gastric disorders in humans. The mechanism coupling the brain to the stomach underlying stress-induced gastric dysfunction has remained elusive. Here, we show that the stomach directly receives acetylcholinergic inputs from the dorsal motor nucleus of the vagus (ACh), which are innervated by serotonergic neurons in the dorsal raphe nucleus (5-HT). Microendoscopic calcium imaging and multi-tetrode electrophysiological recordings reveal that the 5-HT → ACh → stomach circuit is inhibited with chronic stress accompanied by hypoactivate gastric function. Artificial activation of this circuit reverses the gastric dysfunction induced by chronic stress in both male and female mice. Our study demonstrates that this 5-HT → ACh → stomach axis drives gastric dysfunction associated with stress, thus providing insights into the circuit basis for brain regulation of the stomach.