Brain-gut communication via vagus nerve modulates conditioned flavor preference.

It is well known that the postingestive effect modulates subsequent food preference. We previously showed that monosodium L-glutamate (MSG) can increase flavor preference by its postingestive effect. The neural pathway involved in mediating this effect, however, remains unknown. We show here the role of the vagus nerve in acquiring this learned flavor preference and in the brain's response to intragastric glutamate infusion. Adult rats with an intragastric cannula underwent total abdominal branch vagotomies (TVX), common hepatic branch vagotomies (HVX), total abdominal branch vagotomies with the common hepatic branch intact (TVXh), or sham operations (Sham). Following recovery, rats were subjected to a conditioned flavor preference paradigm, in which they drank a flavored solution (CS+) paired with intragastric MSG or another flavored solution (CS-) paired with intragastric distilled water. After conditioning, the Sham and HVX groups demonstrated significantly higher intake of CS+ than CS-, whereas the TVXh and TVX groups showed no significant differences. We then conducted an fMRI study to identify the brain areas that responded to the intragastric glutamate in each group. In the Sham, HVX and TVXh groups, intragastric MSG significantly increased the BOLD intensity in the nucleus of the solitary tract. The amygdala, hippocampus and lateral hypothalamus were also activated in the Sham and HVX groups but not in the TVXh and TVX groups. These results indicate that the abdominal vagus nerve is necessary for acquiring preference and that the lateral hypothalamus and limbic system could be key areas for integrating the information on gut glutamate and oronasal stimuli.