Gastrointestinal tract innervation of the mouse: afferent regeneration and meal patterning after vagotomy

Abstract

Mice, with the variety of genotypes they provide, should be particularly useful for studies of growth factors and gene products in regeneration of autonomic pathways such as the vagus nerve. To provide a foundation for examinations of mouse vagal reorganization, two experiments assessed the rate, extent, and accuracy of afferent reinnervation of the stomach after vagotomy and related these patterns to feeding behavior. In experiment 1, the pattern of afferent regrowth into the gut after unilateral truncal vagotomy was characterized by labeling of these afferents with wheat germ agglutinin-horseradish peroxidase and Micro-Ruby. Regenerating neurites had reached and, in some cases, already reinnervated the stomach by 4 wk after axotomy. By 8 wk, regrowth was more extensive, and many fibers had redifferentiated terminals in the smooth muscle. By 16 wk, vagal projections had reached or exceeded normal density in the corpus, density in the forestomach was still reduced, and regrowth in the antrum was minimal. At all time points, not only appropriate terminals, but also growth cones and aberrant endings, were observed. In experiment 2, meal patterns of vagotomized mice were evaluated using a solid diet over the period of regeneration; cholecystokinin suppression of a liquid meal after unilateral and bilateral truncal vagotomies was also evaluated. Unilaterally, as well as bilaterally, vagotomized animals ate smaller and more frequent meals. These disturbed patterns became more pronounced in the first 8 wk after vagotomy, during regeneration. Cholecystokinin inhibition of intake was attenuated by bilateral, but not unilateral, vagotomy. Overall, the spatial and temporal patterns of structural and functional changes observed during regeneration verify that the mouse provides a useful preparation for examining the control of vagal plasticity.