Functional characterization and classification of enteric neurons, and regional differences in neural control of digestive functions

We provide an account of enteric neuron types and their roles throughout the digestive tract. It is notable that CNS control is essential in the esophagus and has greater importance in the stomach and distal colon than in the small intestine. CNS control is not essential for the small intestine. Enteric neuron phenotypes and ENS circuits have been determined in detail in the small intestine and colon, but for only two functions, muscle movement and fluid secretion. We discuss neurons controlling other ENS functions, in particular control of neuro-immune interactions and control of nutrient transport. In the small intestine, key neurons include intrinsic primary afferent neurons (IPANs), muscle motor neurons and secretomotor neurons. Neurons for control of acid, enzyme and hormone secretion occur in the stomach, but, except for the muscle motor neurons, gastric neuron types are poorly understood, and information on equivalences of structural and functional types with types defined by expression analysis is lacking. There are substantial gaps in knowledge of esophageal circuitries. IPANS occur in the colon, but whether they occur in the stomach and esophagus is uncertain. We also discuss species differences in organisation of the enteric plexuses and chemical coding of functionally identified neurons. We conclude that there are at least 26 definable enteric neuron types, and several subtypes. There is a need for more in-depth correlated functional and gene expression studies in order to reach a fuller understanding of the physiological roles of the ENS, its constituent neurons and its central connections.