The role of gastrointestinal vagal afferents in the control of food intake: current prospects.

Meals are the functional units of food intake in humans and mammals, and physiologic approaches to understanding the controls of meal size have demonstrated that the presence of food in the upper gastrointestinal tract plays a critical role in determining meal size. The vagus nerve is the primary neuroanatomic substrate in the gut-brain axis, transmitting meal-related signals elicited by nutrient contact with the gastrointestinal tract to sites in the central nervous system that mediate ingestive behavior. This article describes progress in examining the role of the vagal gut-brain axis in the negative-feedback control of meal size from four perspectives: neuroanatomic, neurophysiologic, molecular, and behavioral. Vagal afferents are strategically localized to be sensitive to meal-related stimuli, and their central projections are organized viscerotopically in the caudal brainstem. Vagal afferents are sensitive to mechanical, chemical, and gut and peptide meal-related stimuli and can integrate multiple such modalities. Meal-elicited gastrointestinal stimuli activate distinct patterns of c-fos neural activation within caudal brainstem sites, where gut vagal afferents terminate. Results of selective chemical and surgical vagal deafferentation studies have refined our understanding of the sites and types of critical gastrointestinal feedback signals in the control of meal size. Recent behavioral, molecular, and neurophysiologic data have demonstrated brainstem sites where centrally acting neuropeptides may modulate the processing of gut vagal afferent meal-related signals to alter feeding. Investigations of the structure and function of splanchnic visceral afferents and enterics and characterization of the integrative capacities of the hindbrain and forebrain components of the gut-brain axis are critical next steps in this analysis.