Terence Smith Ph.D.

Professor

Cellular and Molecular Pharmacology & Physiology | Department of Physiology and Cell Biology

Terence Smith

Contact Terence Smith Ph.D.


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Terence Smith

Biography

Professor Terence Smith is Director of the Dynamic Imaging Core in the Department of Physiology and Cell Biology., University of Nevada School of Medicine, Reno, Nevada USA. He was honored with the Janssen Award (AGA) for excellence in basic research in Digestive Sciences in 2003.

He graduated (1970) with a BSc (Hons-Physics) and MSc (Solid State Physics) from the University of Sussex, UK. Following studies in low temperature physics and biophysics, he became a Ph.D. student of Professors Mollie Holman and David Hirst (who first classified enteric AH and S neurons) in the Neuroscience group at Monash University, Australia. Following graduation (1984), he had Post Doctoral Fellowships with Kenton Sanders (Reno) and Marcello Costa and John Furness (Adelaide). He then became an Assistant Professor at the University of Virginia, returning to Reno as an Associate Professor in 1995. Dr. Smith has published over 100 well cited articles in prestigious journals, including Nature.

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.