The majority of inferior mesenteric ganglion (IMG) neurons receive afferent synaptic input from a subset of enteric neurons distributed throughout the colon. This major afferent pathway targets sympathetic IMG neurons which control motility and intestinal secretion. NADPH- diaphorase and neuronal nitric oxide synthase are localized in the majority of colonofugal neurons which project to the IMG. There is currently little information on the role of NO in the IMG. Many of the actions of NO in gut and vascular smooth muscle appear to be due to elevation of cGMP through activation of NO-sensitive soluble guanylate cyclase. There are no comparable studies for IMG neurons. One objective of this proposal is to provide an understanding of how NO modulates the synaptic gain of the colon-IMG reflex, and the role of NO-generated cGMP in this reflex pathway. Heme oxygenase 2, the key enzyme for production of CO, is present in the IMG. Little is known regarding the role of CO in prevertebral ganglion function. The second objective, therefore. is to investigate the role of CO in the IMG by localizing the distribution of heme-oxygenase 2, measuring CO production by the IMG, and by evaluating the effect of CO on ganglion cell excitability and synaptic transmission. Lastly. the structural morphology of the neurons which comprise the colon-IMG reflex is not well understood. Thus, the third aim is to reconstruct in 3D using laser scanning confocal microscopy the neurons of the colon-IMG reflex. the surface distribution of putative synaptic regions. and the distribution of specific receptor clusters known to regulate the reflex. The methods used include intracellular microelectrode recordings, immunohistochemical staining, radioimmunoassay, radiothin layer chromatography, and confocal laser scanning microscopy. This work is expected to augment knowledge of the circuits of the peripheral nervous system which modulate fluid loading and motility of the colon.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Hamilton, Frank A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mayo Clinic, Rochester
United States
Zip Code
Matsuda, Nilce Mitiko; Miller, Steven M; Szurszewski, Joseph H (2010) Heme-oxygenase-2 immunolabelling in pig jejunum. Acta Histochem 112:402-6
Vernino, Steven; Ermilov, Leonid G; Sha, Lei et al. (2004) Passive transfer of autoimmune autonomic neuropathy to mice. J Neurosci 24:7037-42
Sha, Lei; Miller, Steven M; Szurszewski, Joseph H (2004) Morphology and electrophysiology of neurons in dog paraventricular nucleus: in vitro study. Brain Res 1010:95-107
Ermilov, Leonid G; Schmalz, Philip F; Miller, Steven M et al. (2004) PACAP modulation of the colon-inferior mesenteric ganglion reflex in the guinea pig. J Physiol 560:231-47
Miller, Steven M; Szurszewski, J H (2003) Circumferential, not longitudinal, colonic stretch increases synaptic input to mouse prevertebral ganglion neurons. Am J Physiol Gastrointest Liver Physiol 285:G1129-38
Ermilov, L G; Miller, S M; Schmalz, P F et al. (2003) Morphological characteristics and immunohistochemical detection of nicotinic acetylcholine receptors on intestinofugal afferent neurones in guinea-pig colon. Neurogastroenterol Motil 15:289-98
Miller, S M; Szurszewski, J H (2002) Relationship between colonic motility and cholinergic mechanosensory afferent synaptic input to mouse superior mesenteric ganglion. Neurogastroenterol Motil 14:339-48
Sha, L; Westerlund, J; Szurszewski, J H et al. (2001) Amplitude modulation of pulsatile insulin secretion by intrapancreatic ganglion neurons. Diabetes 50:51-5
Ermilov, L G; Miller, S M; Schmalz, P F et al. (2000) The three-dimensional structure of neurons in the guinea pig inferior mesenteric and pelvic hypogastric ganglia. Auton Neurosci 83:116-26
Miller, S M (2000) Control of peripheral sympathetic prevertebral ganglion neurones by colonic mechanosensory afferents. Gut 47 Suppl 4:iv28-9; discussion iv36

Showing the most recent 10 out of 39 publications