Parallel gut-to-brain pathways orchestrate feeding behaviors

The caudal nucleus of the solitary tract (cNTS) in the brainstem serves as a hub for integrating interoceptive cues from diverse sensory pathways. However, the mechanisms by which cNTS neurons transform these signals into behaviors remain debated. We analyzed 18 cNTS-Cre mouse lines and cataloged the dynamics of nine cNTS cell types during feeding. We show that Th⁺ cNTS neurons encode esophageal mechanical distension and transient gulp size via vagal afferent inputs, providing quick feedback regulation of ingestion speed. By contrast, Gcg⁺ cNTS neurons monitor intestinal nutrients and cumulative ingested calories and have long-term effects on food satiation and preference. These nutritive signals are conveyed through a portal vein-spinal ascending pathway rather than vagal sensory neurons. Our findings underscore distinctions among cNTS subtypes marked by differences in temporal dynamics, sensory modalities, associated visceral organs and ascending sensory pathways, all of which contribute to specific functions in coordinated feeding regulation.