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- Ph.D., Neuroscience, Monash University Australia, 1984
- M.S., Solid State Physics, University of Sussex, United Kingdom, 1970
- B.S., Hons-Physics, University of Sussex, United Kingdom, 1970
The major thrust of our laboratory is how the intrinsic (enteric) nervous system within the gut wall regulates bowel motility and secretion. In particular, to determine how the enteric) nervous system and intrinsic pacemaker networks regulate motility in different regions of the gastrointestinal (GI) tract. To do this we use a variety of techniques that include: intracellular microelectrode recordings from myenteric neurons and smooth muscle; patch clamping of functionally identified enteric neurons (DiI retrograde labeling); dot marker arrays and spatio-temporal maps to tract gut movements and fluorescent imaging of pacemaker cells and enteric neurons. In particular, we are using fluorescent imaging techniques to better understand the spread of excitability through intestinal smooth muscle, Interstitial Cells of Cajal (ICC) and enteric neurons. Our aim is to integrate activity in all these networks in order to understand how they interact with one another and generate the different motility patterns of the GI tract.
In particular, we are using fluorescent imaging techniques to better understand the spread of excitability through intestinal smooth muscle, Interstitial Cells of Cajal (ICC) and enteric neurons. Our aim is to integrate activity in all these networks in order to understand how they interact with one another and generate the different motility patterns of the GI tract.
Our group has proposed several paradigm shifts in GI physiology, including:
1) the two muscle layers of the muscularis externa are synchronously (not reciprocally) activated during peristaltic reflexes;
2) there are different functional classes of myenteric sensory interneurons that respond to either circumferential or longitudinal stretch;
3) The large intestine contains sensory AH neurons that respond to increases in muscle tension and sensory interneurons that respond to increases in muscle stretch. Therefore, these systems are analogous to Golgi tendon organs and muscle spindles in the somatic nervous system.
4) there is muscle tone dependent and stretch dependent peristalsis;
5) fecal matter regulates the propagation of colonic MMCs by generating local reflex activity.
6) most significantly, we have recently discovered another reflex in the gut wall that underlies colonic accommodation and slow transit. Transit through the human colon is extremely slow (30-48hrs) compared to that through the small intestine (2-4hrs), despite the colons much shorter length. This inhibitory reflex is triggered by colonic elongation that causes intrinsic sensory interneurons that respond to longitudinal stretch to release nitric oxide to inhibit nerve circuits underlying peristalsis. This inhibitory reflex is a natural physiological response triggered by accumulating fecal matter that elongates the colon.