Optical Approaches to Understanding Enteric Circuits Along the Radial Axis.

Abstract

The gastrointestinal tract operates in a highly dynamic environment. The gut is typically exposed to continually changing and highly convoluted luminal compositions comprising not only ingested content but also a multitude of resident microbes and microbial factors. It is therefore critical that the gut is capable of distinguishing between nutritious components from noxious substances. This is facilitated by specialized cellular sensory machinery that are in place in the intestinal epithelium and the ENS. However, the specific chemosensory processes and enteric neuronal pathways that enable the gut to discern and respond appropriately to different chemicals remain unclear. A major hurdle in studying the neural processing of luminal information has been the complex spatial organization of the mucosal structures and their innervation along the radial axis. Much of our current knowledge of enteric neuronal responses to luminal stimuli stems from studies that used semi-dissected guinea pig small intestine preparations with the mucosa and submucosa removed in one-half in order to record electrical activity from exposed myenteric neurons or in the circular muscle. Building on this, we ultimately strive to work towards integrated systems with all the gut layers intact. With advanced microscopy techniques including multiphoton intravital imaging, together with transgenic technologies utilizing cell-type specific activity-dependent reporters, we stand in good stead for studying the ENS in more intact preparations and even in live animals. In this chapter, we highlight recent contributions to the knowledge of sensory gut innervation by the developing and mature ENS. We also revisit established work examining the functional connectivity between the myenteric and submucosal plexus, and discuss the methodologies that can help advance our understanding of the enteric circuitry and signaling along the mucosa-serosa axis.