Computation Within and Beyond the Brain - Uncovering Brain-Body-Wide Communication Networks through Imaging Cellular Activity of All Cells in a Vertebrate

Animals are dynamical systems possessing a wide range of capabilities mediated by interactions between their constitutive cells. The brain, central integrator and coordinator of bodily output, solves problems in the context of bodily needs, driven by external environmental signals and internal bodily signals. While neuroscience has progressed in the ability to measure neurons and environment at ever great scale and resolution, our ability to measure activity within the rest of the body and relate these to neuronal computation remains limited. Here, we extend the principles and tools of neuroscience to the rest of the cells in the body. We develop Whole Brain-body cellular activity Imaging (WBI), a paradigm for imaging cellular activity across the entire larval zebrafish in vivo. We analyzed cellular activity throughout the entire organism which was made possible by advances on multiple fronts: engineering zebrafish expressing genetically encoded calcium sensors in nearly all body cells, using fast volumetric fluorescence imaging and developing novel machine learning algorithms for volume registration and activity analysis. We find that, like neurons, the rest of the cells across the body exhibit a wide range of cellular dynamics. WBI reveals spontaneous and stimulus-driven coordinated activity between the brain and organs such as muscles, skin, and vasculature. It uncovers synergies between muscle groups and a topological relationship between hindbrain neurons and smooth muscle along the gut and, activity in non-neuronal cells that predicts periods of prolonged motor inactivity. During hypoxia, WBI captures coupling between the brain, gut, and redirection of blood flow away from the digestive system through brain-controlled vessel constriction. WBI enables unprecedented access and insights into coordination of dynamics across all cells of the vertebrate body, opening new avenues for studying brain-body-wide computation.