Sub-diaphragmatic vagal afferent integration of meal-related gastrointestinal signals.

We have established a method to investigate the range of mechanical, nutrient chemical and peptidergic meal-related stimuli t hat may generate vagal afferent neurophysiological signals critical to the negative feedback control of food intake in the rat. We have identified populations of fibers that respond with increased neurophysiological discharge rates to gastric loads, duodenal loads, and close celiac arterial administration of a brain-gut peptide, cholecystokinin. Load-sensitive fibers with gastric and duodenal mechanoreceptive fields are able to integrate information arising from mechanical and peptidergic stimulation, where cholecystokinin octapeptide (CCK) administration potentiates subsequent responses to distending loads, and synergizes with distending loads to produce greater excitation than either load stimulus alone or peptide stimulation alone. In addition, we have identified situations where the duodenal presence of nutrients modifies the vagal afferent activity of gastric load-sensitive fibers. Thus, our approach can mimic the temporal and spatial distribution of meal-related stimuli in the gut, and reveals the potential for nutrients in one gastrointestinal compartment to affect neutral signals arising from another gut compartment.