Whole-brain, all-optical interrogation of neuronal dynamics underlying gut and vascular interoception in zebrafish.

To select behaviors appropriate to their circumstances and needs, animals integrate information about the external environment with information about the state of their bodies, derived from sensing and processing internal signals (interoception). However, the brain-wide circuit activity underlying interoception and its integration with sensorimotor processing remains unclear, partly because of technical barriers to accessing whole-brain activity at the cellular level during physiological perturbations. We developed an all-optical system for whole-brain neuronal imaging in behaving larval zebrafish during optical uncaging of gut- or bloodstream-targeted nutrients and visuo-motor stimulation. Widespread neural activity throughout the brain encoded nutrient delivery, unfolding on multiple timescales across many peripheral and central regions. Evoked activity depended on delivery location and occurred in response to both amino acids and D-glucose, but not L-glucose. Many gut responsive neurons also responded to swimming and visual stimuli, with brainstem areas primarily integrating gut and motor signals and midbrain regions integrating jointly gut, visual, and motor signals. This platform links body-brain communication studies to brain-wide neural computation in awake, behaving vertebrates.