Experimental data supporting a novel hypothesis for the rhythmic initiation of proximal colon motor complexes

Current models of colon motility are largely based on studies of distal regions where distension-induced neural peristalsis predominates, but the proximal colon significantly differs in terms of cellular organization and its rhythmic motor activity that continues without external sensory input, emphasizing the need to define the unique mechanisms utilized by the proximal colon. With the long-term goal of developing a new model for the rhythmic initiation of proximal colon motor complexes (CMCs), we used in situ calcium imaging to define activity patterns in key players for colon motility [i.e., submucosal interstitial cells of Cajal (ICC-SM) and myenteric neurons of the enteric nervous system (ENS)], while simultaneously monitoring motor output in the proximal mouse colon. We observed repeated patterns of activity in ICC-SM and ENS myenteric neurons during the intervals between CMCs that could be used to predict the timing of subsequent CMC events. Based on our findings, we propose a novel hypothesis that cyclical interactions between the ENS and ICC-SM act as an intrinsic pattern generator for the rhythmic initiation of proximal CMCs.