Cerebellar Neurodynamics Predict Decision Timing and Outcome on the Single-Trial Level
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Abstract
Goal-directed behavior requires the interaction of multiple brain regions. How these regions and their interactions with brain-wide activity drive action selection is less understood. We have investigated this question by combining whole-brain volumetric calcium imaging using light-field microscopy and an operant-conditioning task in larval zebrafish. We find global, recurring dynamics of brain states to exhibit pre-motor bifurcations toward mutually exclusive decision outcomes. These dynamics arise from a distributed network displaying trial-by-trial functional connectivity changes, especially between cerebellum and habenula, which correlate with decision outcome. Within this network the cerebellum shows particularly strong and predictive pre-motor activity (>10 s before movement initiation), mainly within the granule cells. Turn directions are determined by the difference neuroactivity between the ipsilateral and contralateral hemispheres, while the rate of bi-hemispheric population ramping quantitatively predicts decision time on the trial-by-trial level. Our results highlight a cognitive role of the cerebellum and its importance in motor planning.
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A brainstem integrator for self-localization and positional homeostasisPreprint
Yang, E., Zwart, M., Rubinov, M., James, B., Wei, Z., Narayan, S., Vladimirov, N., Mensh, B. D., Fitzgerald, J. E., & Ahrens, M. B. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.26.468907 · Cited by 5 · see citing works
Functional and pharmacological analyses of visual habituation learning in larval zebrafishPreprint
Lamiré, L.-A., Haesemeyer, M., Engert, F., Granato, M., & Randlett, O. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.17.496451 · Cited by 5 · see citing works
Self-citationNeural correlates of future volitional action in DrosophilaPreprint
Brezovec, L. E., Berger, A. B., Druckmann, S., & Clandinin, T. R. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.08.556917 · Cited by 5 · see citing works
Neural sequences underlying directed turning in Caenorhabditis elegans
Kramer, T. S., Wan, F. K., Pugliese, S. M., Atanas, A. A., Pradhan, S., Hiser, A. W., Godinez, L., Luo, J., Bueno, E., Felt, T. E., et al. (2026) · Nature Neuroscience · doi:10.1038/s41593-026-02257-5 · Cited by 4 · see citing works
Distinct distributed neural dynamics predict pallium-dependent social approach
Lifshitz, I., Prag, A., Livneh, N., Moshkovitz, M., Karmi, A., & Avitan, L. (2026) · Nature Communications · doi:10.1038/s41467-026-71666-8 · Cited by 3 · see citing works
Cerebellar Purkinje cells control posture in larval zebrafish (Danio rerio)
Auer, F., Nardone, K., Matsuda, K., Hibi, M., & Schoppik, D. (2025) · eLife · doi:10.7554/elife.97614.3 · Cited by 3 · see citing works
Short-term memory by distributed neural network oscillators in a simple nervous system
Dunn, R. L., Costello, C. M., Borchardt, J., Sprague, D., Chiu, G. C., Miller, J. M., L’Étoile, N. D., & Kato, S. (2025) · Current Biology · doi:10.1016/j.cub.2025.10.018 · Cited by 3 · see citing works
Inhibition drives habituation of a larval zebrafish visual responsePreprint
Lamiré, L.-A., Haesemeyer, M., Engert, F., Granato, M., & Randlett, O. (2023) · eLife · doi:10.7554/elife.84926.1 · Cited by 3 · see citing works
Self-citationDevelopmental synaptic pruning sharpens neural representations for predictive motor controlPreprint
Verma, S., Chandra, S., Narayanan, S., Pathak, S., & Thirumalai, V. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.01.630979 · Cited by 3 · see citing works
Modulation of habenula axon terminals supports action-outcome associations in larval zebrafishPreprint
Paoli, E., Palieri, V., Shenoy, A., & Portugues, R. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.13.638047 · Cited by 3 · see citing works
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Altered locomotion and anxiety after exposure to SiO2 nanoparticles in larval zebrafish
Shen, P. Y., Wu, J., Pu, G., Huang, K., & Lin, Q. (2025) · Scientific Reports · doi:10.1038/s41598-025-02599-3 · Cited by 2 · see citing works
Self-citationFrom Cerebellar Genes to Behaviors in Zebrafish
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Ramp-to-threshold dynamics in a hindbrain population controls the timing of spontaneous saccades
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FABEL: Forecasting Animal Behavioral Events with Deep Learning-Based Computer VisionPreprint
Catto, A., O’Connor, R., Braunscheidel, K. M., Kenny, P. J., & Shen, L. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.15.584610 · Cited by 2 · see citing works
Whole-brain neural substrates of behavioral variability in the larval zebrafishPreprint
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Self-citationNeural Sequences Underlying Directed Turning in C. elegansPreprint
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Cerebellar involvement in self-timingPreprint
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Modulation of habenula axon terminals supports action-outcome associations in larval zebrafish
Paoli, E., Palieri, V., Shenoy, A., & Portugues, R. (2026) · Nature Communications · doi:10.1038/s41467-026-76267-z · Cited by 4 · see citing works
Cerebellum and Decision-Making
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States Are A-Changing, Complex Spikes Proclaim
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Ramp-to-Threshold Dynamics in a Hindbrain Population Controls the Timing of Spontaneous SaccadesPreprint
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Deducing ensemble dynamics and information flow from the whole-brain imaging dataPreprint
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Progress on Computational Ethology
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C. elegans behaviour and brain dynamics; a physical exploration
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Functional and pharmacological analyses of visual habituation learning in larval zebrafishPreprint
Lamiré, L.-A., Haesemeyer, M., Engert, F., Granato, M., & Randlett, O. (2023) · eLife · doi:10.7554/elife.84926.2
Self-citationKasahara, K., Hikishima, K., Nakata, M., Tsurugizawa, T., Higo, N., & Doya, K. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.26.564278
Whole-brain neural substrates of behavioral variability in the larval zebrafishPreprint
Manley, J., & Vaziri, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.03.583208
Self-citationZarei, M., Xie, D., Jiang, F., Bagirov, A., Huang, B., Raj, A., Nagarajan, S. S., & Guo, S. (2022) · Figshare · doi:10.6084/m9.figshare.19582444
Whole-brain neural substrates of behavioral variability in the larval zebrafishPreprint
Manley, J., & Vaziri, A. (2024) · eLife · doi:10.7554/elife.97014
Self-citationCerebellar Purkinje Cells Control Posture in Larval Zebrafish (Danio rerio)Preprint
Auer, F., Nardone, K., Matsuda, K., Hibi, M., & Schoppik, D. (2024) · eLife · doi:10.7554/elife.97614.1
Cerebellar Purkinje Cells Control Posture in Larval Zebrafish (Danio rerio)Preprint
Auer, F., Nardone, K., Matsuda, K., Hibi, M., & Schoppik, D. (2025) · eLife · doi:10.7554/elife.97614.2
- Authors
- Lin, Q., Manley, J., Helmreich, M., Schlumm, F., Li, J. M., Robson, D. N., Engert, F., Schier, A., Nöbauer, T., & Vaziri, A.
- Affiliations
- Rockefeller University (US)
- Research Institute of Molecular Pathology (AT)
- Harvard University (US)
- Corresponding author
- Vaziri, Alipasha
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 180
- Issue
- 3
- Pages
- 536-551.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7299501
- OpenAlex
- W3000696985
- Cited by
- 122
- References
- 140
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 16 · 2023: 16 · 2022: 31 · 2021: 22 · 2020: 9 · 2018: 1
- FWCI
- 10.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- edoc (University of Basel) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Gordon and Betty Moore Foundation (2919.01)
- Intelligence Advanced Research Projects Activity (D16PC00002)
- National Institutes of Health (1RF1NS110501, DP1HD094764, R24NS086601, 1RF1 NS113251, R25GM067110, R01NS049319, 5U01NS103488, U19NS104653, 2R44OD024879)
- Simons Foundation (SCGB 542973)
- National Science Foundation (DBI-1707408, PHY-1748958)
- Leon Levy Foundation
- Kavli Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- cerebellum, decision timing, decision outcomes, zebrafish larvae, calcium imaging, light field microscopy, cerebellar granule cells, habenula, bifurcation dynamics, functional connectivity, hemispheric lateralization, motor planning, action selection, operant conditioning
- MeSH terms
- Animals, Behavior, Animal, Brain Mapping, Cerebellum, Cognition, Conditioning, Operant, Decision Making, Goals, Hot Temperature, Larva, Motor Activity, Movement, Neurons, Psychomotor Performance, Reaction Time, Rhombencephalon, Zebrafish, Habenula, Cerebrum
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