Understanding normal and dysfunctional body weight regulation requires an elucidation of the factors that initiate, maintain, and terminate an individual meal. Each of these aspects of meal consumption is influenced by oral (gustatory) and post-oral (post-ingestive) factors, whose separate and integrative contributions to satiety are not fully understood. The proposed experiments will focus on the integrative nature of this relationship. Following ingestion and the initiation of digestion, nutrients trigger a variety of post-ingestive signals from upper gastrointestinal and vascular sites that terminate feeding, produce satiety, and reduce the appetitive nature of food. Recent studies have suggested that satiety may be accompanied by a decrement in taste-elicited activity in the orbitofrontal cortex, but the link between post-ingestive feedback and satiety-induced changes in taste responsivity has not been addressed either directly or systematically. The proposed experiments will examine how post-ingestive feedback (gastric distention, duodenal glucose infusion, venous glucose infusion) modulates taste-elicited activity in the orbitofrontal cortex. Collectively, these experiments will provide the first systematic neurophysiological investigation of how gustatory and visceral factors contribute to the etiology of satiety and the control of food intake. These data may expedite development of successful strategies for diagnosis and treatment of various eating and metabolic disorders.