Trust Your Gut: Developing A Data Driven Model for Mouse Colon Motility Dynamics

Colon motility, the spontaneous self-generated movement and motion of the colon muscle and its cells, is produced by activity in different types of cells such as myenteric neurons of the enteric nervous system (ENS), neurons of the autonomic nervous system (ANS) and interstitial cells of Cajal (ICC). Two colon motor patterns measured experimentally are colonic motor complexes (CMC) often associated with the propulsion of fecal contents, and ripple contractions which are involved in mixing and absorption. How ICC and neurons of the ENS and ANS interact to initiate and influence colon motility is still not completely understood. This makes it difficult to develop new therapies to restore function in pathological conditions. Using data analysis machine learning techniques such as k-means clustering, we have found three activity patterns of neuronal behavior at different regions of the CMC cycle suggesting different functional classes of myenteric ENS neurons with unique roles for CMC initiation. From this, we have developed a model that reproduces the global dynamics observed in optogenetic and calcium measurements of mouse colons. This study presents strong evidence from experimental and computational approaches that cyclical ENS-ICC interactions form the intrinsic pattern generator for rhythmic CMC initiation in proximal colon.