Extended Data Fig. 10: Simplified schematic of proposed model for the detection of luminal nutrient information by the ENS of the mouse small intestine.

a, Luminal nutrients are first detected at the mucosal surface by enteroendocrine (EEC) cells, which include EC cells, as well as other epithelial cells such as enterocytes. The basolateral release of 5-HT from EC cells after nutrient activation then stimulates 5-HT₃ receptor (5-HT₃R)-expressing intrinsic sensory nerve endings that supply the villi. Other mucosal mediators that activate intrinsic nerve endings and their corresponding neuronal receptors have yet to be established. Schematic adapted from ref. ³ under a Creative Commons licence CC BY 4.0. b, Intrinsic sensory neurons (IPANs) that project to the mucosa reside in the MP and respond mainly to the luminal stimulus. Interneurons and motor neurons of ascending excitatory and/or inhibitory descending pathways may be activated secondarily through nicotinic transmission. c, IPANs are also found in the SMP and respond directly to luminal stimuli. Other submucosal (secretomotor) neurons respond secondarily through interneurons and/or myenteric sensory neurons, and their responses are mediated by nicotinic transmission.