Properties and functions of transcriptionally distinct enteric neurons

The influence of the nervous system on the intestine is carried out by a combination of enteric, sensory, and autonomic innervation. However, disambiguating the functions of these physiologically distinct intestine-innervating neuronal populations has been a challenge. Here, we develop a collection of mouse genetic tools that enable precise manipulation and examination of intestine-innervating neurons, particularly those in the enteric nervous system, which represent the most frequent of the intestine-innervation neural populations. We report that an array of transcriptionally distinct enteric neuron subpopulations has distinct morphological specializations and influences on intestinal function, including controlling fecal output, fecal hydration, and food intake. We also report that subpopulations within the enteric nervous system require extrinsic innervation to exert control over intestinal transit or food intake. Collectively, these genetic approaches enable interrogation of the enteric nervous system and further study of its interactions with broader neural networks in the body.