We have established a method to investigate the range of mechanical, n
utrient chemical and peptidergic meal-related stimuli that may generat
e vagal afferent neurophysiological signals critical to the negative f
eedback control of food intake in the rat. We have identified populati
ons of fibers that respond with increased neurophysiological discharge
rates to gastric loads, duodenal loads, and close celiac arterial adm
inistration of a brain-gut peptide, cholecystokinin. Load-sensitive fi
bers with gastric and duodenal mechanoreceptive fields are able to int
egrate information arising from mechanical and peptidergic stimulation
, where cholecystokinin octapeptide (CCK) administration potentiates s
ubsequent responses to distending loads, and synergizes with distendin
g loads to produce greater excitation than either load stimulus alone
or peptide stimulation alone. In addition, we have identified situatio
ns where the duodenal presence of nutrients modifies the vagal afferen
t activity of gastric load-sensitive fibers. Thus, our approach can mi
mic the temporal and spatial distribution of meal-related stimuli in t
he gut, and reveals the potential for nutrients in one gastrointestina
l compartment to affect neural signals arising from another gut compar
tment.