Neurogastroenterology Laboratory

Research Projects

Sensation from Gut

Our studies on the different functional classes of extrinsic sensory neurons to the gut continue. These neurons are important in our daily lives as they are responsible for initiating the sensations that we all experience from our gastrointestinal tracts. They also activate reflex pathways which we may not be conscious of. We have developed a series of techniques that make it possible to identify the morphology of sensory endings within the gut wall and identify their structure and location. This is leading to a comprehensive description of the different types of sensory neurons that convey information from the gut to the central nervous system, in which we can relate their fine structure to their mechanical and chemical sensitivity for the first time. Over the last decade, we have characterised stretch receptors in the stomach and oesophagus (called IGLEs) that provide sensations of fullness after a meal. We have identified similar low threshold sacral mechanoreceptors in the rectum that have the characteristics expected of sensory neurons that give rise to the sense of “urgency” that we are all familiar with. We also identified the major populations of high threshold mechano-nociceptors (the pain pathways). More recently we have concentrated on two other classes of mechanoreceptors:

1. We have identified sensory endings within the upper gut of a distinct class of high threshold mechanosensitive afferent nerves (first identified in 2005 by other authors). These have quite different responses from low threshold mechanoreceptors and do not use IGLEs as their transduction sites. Their endings lie within the muscle layers (rather than in enteric ganglia) and resemble “intramuscular arrays” that were first described by Berthoud and Powley in the early 1990s.
2. We have also identified the endings of a distinct class of sensory neuron in the colon that respond to both mucosal deformation and either stretch or contraction of the muscle of the gut wall. These “muscular mucosal” sensory neurons are found in both rectum and distal colon. Their endings lie in the subepithelial plexus and are able to respond to a wide range of low intensity mechanical stimuli. They probably respond to shear forces generated by the propulsion of content along the distal gut.

Viscerofugal neurons in the mammalian gut

This subject is being investigated by Tim Hibberd. These neurons have cell bodies in the gut and project to sympathetic ganglia, where they excite sympathetic post-ganglionic neurons to the gut. We have identified patterns of activity of single viscerofugal neurons and demonstrated that they contribute to recordings from mesenteric nerves. We are currently characterising their mechanical sensitivity and synaptic inputs.

Smooth muscle activity in the gut

This project is being undertaken by Simona Carbone. She is investigating why preparations of smooth muscle in vitro often require a “warm-up” period before they display normal responses to drugs and electrical/neural stimulation. It appears that gap junction coupling between smooth muscle cells is often impaired in the first 60 minutes in vitro and that this may contribute to their lack of responsiveness. This is being investigated, along with attempts to identify the mechanisms that underlie loss of gap junction function.

Parasympathetic innervation of the distal bowel

This project studies the mechanisms by which parasympathetic nerves affect the motility of the distal bowel, which are particularly important in colonic motility and defecation. We are studying the effects of electrical stimulation of these pathways on patterns of contractility and are examining the extent of branching of these pathways within the wall of the gut. Data to hand indicate that there is a mismatch between the projections of parasympathetic neurons in the gut wall and the distance over which they affect motility, suggesting that they powerfully activate specific enteric neuronal pathways.

Innervation of human gut

Our long term collaboration with Dr David Wattchow in the Discipline of Surgery continues on human gut tissue. We also work in collaboration with Dr Nick Spencer on these projects. We have concentrated, in our laboratory, on the motor behaviour of specimens of human colon in vitro. In particular, we have identified that the patterns of myogenic contraction (in the presence of drugs that block neuronal activity entirely) vary considerably between small specimens of tissue and larger pieces (20 x 40mm). This suggests that the simple published story that myogenic activity is the result of interactions between two pacemaker networks of interstitial cells of Cajal with intrinsic frequencies of 3-6/min and 18- 22/min, may be a simplification.

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Updated October 19, 2011