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The Journal of Neuroscience, November 1, 2001, 21(21):8602-8615
Neurotrophin-4 Deficient Mice Have a Loss of Vagal Intraganglionic Mechanoreceptors from the Small Intestine and a Disruption of Short-Term Satiety
Edward A. Fox1, Robert J. Phillips2, Elizabeth A. Baronowsky2, Mardi S. Byerly1, Sarahlouise Jones2, and Terry L. Powley2 1 Behavioral Neurogenetics Laboratory and 2 Laboratory of Regulatory Psychobiology, Department of Psychological Sciences, Purdue University, West Lafayette, Indiana 47907
Intraganglionic laminar endings (IGLEs) and intramuscular arrays (IMAs) are the two putative mechanoreceptors that the vagus nerve supplies to gastrointestinal smooth muscle. To examine whether neurotrophin-4 (NT-4)-deficient mice, which have only 45% of the normal number of nodose ganglion neurons, exhibit selective losses of these endings and potentially provide a model for assessing their functional roles, we inventoried IGLEs and IMAs in the gut wall. Vagal afferents were labeled by nodose ganglion injections of wheat germ agglutinin-horseradish peroxidase, and a standardized sampling protocol was used to map the terminals in the stomach, duodenum, and ileum. NT-4 mutants had a substantial organ-specific reduction of IGLEs; whereas the morphologies and densities of both IGLEs and IMAs in the stomach were similar to wild-type patterns, IGLEs were largely absent in the small intestine (90 and 81% losses in duodenum and ileum, respectively). Meal pattern analyses revealed that NT-4 mutants had increased meal durations with solid food and increased meal sizes with liquid food. However, daily total food intake and body weight remained normal because of compensatory changes in other meal parameters. These findings indicate that NT-4 knock-out mice have a selective vagal afferent loss and suggest that intestinal IGLEs (1) may participate in short-term satiety, probably by conveying feedback about intestinal distension or transit to the brain, (2) are not essential for long-term control of feeding and body weight, and (3) play different roles in regulation of solid and liquid diet intake.
Key words: autonomic nervous system; food intake; meal pattern; gastrointestinal tract; intraganglionic laminar endings; knock-out mice; myenteric neurons; vagus nerve; visceral afferents
Copyright © 2001 Society for Neuroscience 0270-6474/01/21218602-14$05.00/0
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