Astrocyte-induced internal state transitions reshape brainwide sensory, integrative, and motor computations

Summary Animals rapidly adapt to changing circumstances by shifting how they perceive, integrate, and act. Such flexibility is often attributed to transitions between internal states that exert widespread influence across the brain. Yet the mechanisms that drive state transitions and how they reconfigure brainwide computation remain unclear. Larval zebrafish, when actions are rendered futile by decoupling visual flow feedback from swimming in virtual reality, enter a temporary passive, energy-preserving state. In this state, astrocyte calcium levels are elevated, and swim reinitiation requires greater accumulated visual motion. Using whole-brain, cellular-resolution activity imaging, we observed widespread circuit alterations underlying this disengaged state: neuronal visual responses weakened, visual motion integration over time became dramatically leakier, motor inhibition increased, and motor preparation slowed, together suppressing conversion of sensory evidence into action. Astrocyte calcium rose during futile swimming, tracked the emergence and resolution of these brainwide changes, and was both necessary and sufficient to drive them. Thus, astrocytes orchestrate internal states that profoundly reshape neural computations, most powerfully at intermediate integrative processing stages, to meet changing demands. Highlights Internal state change alters brainwide neuronal processing at every stage of the sensorimotor transformation Effects are most powerful at integrative stages through stimulus memory collapse As state resolves, amplification of sensory representations synergizes with reduced motor inhibition for action reinitiation Astrocyte activity drives these brainwide adaptive shifts in neuronal dynamics Competing Interest Statement The authors have declared no competing interest.