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

Animals sense food quantity and quality to regulate feeding behaviors. 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. Using larval zebrafish, we developed a feeding assay with particles releasing specific nutrients after consumption, demonstrating that EECs regulate nutrient-specific feeding days after gut formation. To determine how post-ingestive signals are encoded along gut-brain circuitry, we developed a microgavage method enabling simultaneous gut stimulation and two-photon imaging. Gut distension alone drove widespread activation and suppression in vagal and dorsal hindbrain neurons. Although nutrient-evoked responses shared temporal features with distension, allyl isothiocyanate elicited slower-onset dynamics. These findings reveal that fast gut-to-brain communication emerges early in life, with distension and aversive chemical cues encoded through distinct temporal dynamics in developing interoceptive circuits.