Brain function relies on communication between large populations of neurons across multiple brain areas, a full understanding of which would require knowledge of the time-varying activity of all neurons in the central nervous system. Here we use light-sheet microscopy to record activity, reported through the genetically encoded calcium indicator GCaMP5G, from the entire volume of the brain of the larval zebrafish in vivo at 0.8 Hz, capturing more than 80% of all neurons at single-cell resolution. Demonstrating how this technique can be used to reveal functionally defined circuits across the brain, we identify two populations of neurons with correlated activity patterns. One circuit consists of hindbrain neurons functionally coupled to spinal cord neuropil. The other consists of an anatomically symmetric population in the anterior hindbrain, with activity in the left and right halves oscillating in antiphase, on a timescale of 20 s, and coupled to equally slow oscillations in the inferior olive.

Internal signals from the body and external signals from the environment are processed by brain-wide circuits to guide behavior. However, the complete brain-wide circuit activity underlying interoception—the perception of bodily signals—and its interactions with sensorimotor circuits remain unclear due to technical barriers to accessing whole-brain activity at the cellular level during organ physiology perturbations. We developed an all-optical system for whole-brain neuronal imaging in behaving larval zebrafish during optical uncaging of gut-targeted nutrients and visuo-motor stimulation. Widespread neural activity throughout the brain encoded nutrient delivery, unfolding on multiple timescales across many specific peripheral and central regions. Evoked activity depended on delivery location and occurred with amino acids and D-glucose, but not L-glucose. Many gut-sensitive neurons also responded to swimming and visual stimuli, with brainstem areas primarily integrating gut and motor signals and midbrain regions integrating gut and visual signals. This platform links body-brain communication studies to brain-wide neural computation in awake, behaving vertebrates.

Brains are notoriously hard to understand, and neuroscientists need all the tools they can get their hands on to have a realistic shot at it. Advances in machine learning are proving instrumental, illustrated by their recent use to shed light on navigational strategies implemented by zebrafish brains.