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

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.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-02-05
DOI
https://doi.org/10.64898/2026.02.05.704034
Primary Topic
Zebrafish Biomedical Research Applications
Type
article
Field-Weighted Citation Impact
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article

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

L. Looger Loren, Jihong Zheng, Xuelong Mi, Behtash Babadi et al.
bioRxiv (Cold Spring Harbor Laboratory)
Zebrafish Biomedical Research Applications
article

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

L. Looger Loren, Jihong Zheng, Xuelong Mi, Behtash Babadi, De Zeeuw Ci, Greg Fleishman, Jing-Xuan Lim, X. William Yang, Alireza Sheikhattar, Yuchen Zhang, Caroline Lei Wee, Sujatha Narayan, Guoqiang Yu, Wei Zheng, Dwight E Bergles, Misha B. Ahrens, Ilya Kolb, James E. Fitzgerald, Mariam Beriashvili, Jeremy P. Hasseman, Ziqiang Wei
article en

Abstract

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.

bioRxiv (Cold Spring Harbor Laboratory)
Northwestern University (US), Agency for Science, Technology and Research (SG), Netherlands Institute for Neuroscience (NL), Allen Institute for Brain Science (US), Royal Netherlands Academy of Arts and Sciences (NL), Howard Hughes Medical Institute (US), Johns Hopkins University (US), Janelia Research Campus (US), Vanderbilt University (US), Discovery Institute (US), Johns Hopkins Medicine (US), Erasmus MC (NL), University of California San Diego (US), NYU Langone Health (US), Allen Institute (US), University of Maryland, College Park (US), Institute of Molecular and Cell Biology (SG), Virginia Tech (US), Erasmus University Rotterdam (NL)
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