The enteric nervous system is a key player in many functions of the gastrointestinal tract, such as transport, digestion and absorption of nutrients and defense against dietary toxins and antigens, and it has been more and more implicated in a number of gastrointestinal diseases. Although the enteric nervous system can act autonomously for local control, its integrative functions are strongly modulated by the central nervous system, in particular via the vagus nerve. Vagal modulation of gastrointestinal function is thus one of the mechanisms by which, on one hand, external and internal events can lead to adaptive and physiologically beneficial effects and, on the other hand, emotional states such as stress can lead to maladaptive effects and disease. This proposal is designed to define the interface between vagal outflow and enteric neurons, the functional units of the enteric nervous system. Some of the questions that should be answered by the proposed studies are: Is vagal outflow organized in a function-specific manner? Is specificity encoded by the neurochemical phenotype of vagal preganglionic neurons of postganglionic, enteric neurons? What are the characteristics of so-called """"""""command neurons"""""""" in the small intestine? What is the functional role of peptides and other co-transmitters in the vagal outflow system? Modern anatomical, molecular- neurochemical, and functional approaches at the cellular and tissue level, as well as an innovative new method to study integrated gut motility will be used. The results will identify the underlying neural substrate and characterize the functional effects of vagal modulation of key gut segments such as the stomach, lower esophageal and pyloric sphincters, small intestine and colon. The findings will lead to new insights about central neural control of normal gastrointestinal function. They may also provide important new clues concerning the effects of physical and emotional stress as well as alcohol on the development of gastric and duodenal lesions and concerning the problem of human gastroesophageal reflux. Finally, the proposed studies will help understand the neural component in the many gastrointestinal motility disorders, gastric stasis induced by acute bacterial infection, and in the longer-term sequelae of inflammatory bowel disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK057242-01
Application #
6055875
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
May, Michael K
Project Start
2000-04-01
Project End
2004-02-28
Budget Start
2000-04-01
Budget End
2001-02-28
Support Year
1
Fiscal Year
2000
Total Cost
$191,743
Indirect Cost
Name
Lsu Pennington Biomedical Research Center
Department
Type
Organized Research Units
DUNS #
City
Baton Rouge
State
LA
Country
United States
Zip Code
70808
Berthoud, Hans-Rudolf; Shin, Andrew C; Zheng, Huiyuan (2011) Obesity surgery and gut-brain communication. Physiol Behav 105:106-19
Zheng, Huiyuan; Patterson, Laurel M; Berthoud, Hans-Rudolf (2005) Orexin-A projections to the caudal medulla and orexin-induced c-Fos expression, food intake, and autonomic function. J Comp Neurol 485:127-42
de Jonge, Wouter J; van der Zanden, Esmerij P; The, Frans O et al. (2005) Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 6:844-51
Berthoud, Hans-Rudolf (2004) Anatomy and function of sensory hepatic nerves. Anat Rec A Discov Mol Cell Evol Biol 280:827-35
Berthoud, Hans-Rudolf (2002) Multiple neural systems controlling food intake and body weight. Neurosci Biobehav Rev 26:393-428
Berthoud, H-R; Hennig, G; Campbell, M et al. (2002) Video-based spatio-temporal maps for analysis of gastric motility in vitro: effects of vagal stimulation in guinea-pigs. Neurogastroenterol Motil 14:677-88
Berthoud, H R; Patterson, L M; Zheng, H (2001) Vagal-enteric interface: vagal activation-induced expression of c-Fos and p-CREB in neurons of the upper gastrointestinal tract and pancreas. Anat Rec 262:29-40
Patterson, L M; Zheng, H; Ward, S M et al. (2001) Immunohistochemical identification of cholecystokinin A receptors on interstitial cells of Cajal, smooth muscle, and enteric neurons in rat pylorus. Cell Tissue Res 305:11-23
Berthoud, H R; Neuhuber, W L (2000) Functional and chemical anatomy of the afferent vagal system. Auton Neurosci 85:17-Jan
Zheng, H; Berthoud, H R (2000) Functional vagal input to gastric myenteric plexus as assessed by vagal stimulation-induced Fos expression. Am J Physiol Gastrointest Liver Physiol 279:G73-81

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