Gut distension evokes rapid neural dynamics in vagal and hindbrain populations of larval zebrafish

Animals sense food quantity and quality to regulate feeding behaviors essential for survival. Enteroendocrine cells (EECs) in the gut epithelium detect luminal distension and nutrients, signaling this information to the brain via vagal sensory neurons. However, how mechanosensory and chemosensory signals are dynamically encoded by gut-brain circuits remains unclear, particularly during early development. Leveraging the transparency and genetic tractability of larval zebrafish, we developed an assay using odorless, alginate-encapsulated particles designed to release nutrients after consumption. Using this approach, we demonstrated that larval EECs regulate nutrient-specific feeding. To determine how these post-ingestive signals are neurally encoded, we developed a microgavage method enabling simultaneous stimulus delivery to the gut and volumetric two-photon calcium imaging. We found that gut distension alone drove widespread activation and suppression in vagal ganglia and dorsal hindbrain, emerging as a dominant enteric signal in early development. Although nutrient-evoked responses shared temporal features with distension, allyl isothiocyanate (AITC)–an aversive compound found in wasabi– elicited distinct neural dynamics with slow onset. These findings reveal that fast gut-to-brain communication emerges early in life, with distension and aversive cues dynamically and differentially encoded in developing interoceptive circuits.