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Peer-reviewedCC BYNature Methods

Voltage imaging of neurons distributed across entire brains of larval zebrafish

  • Zeguan Wang1,2
  • Jie J. Zhang3,4
  • Panagiotis Symvoulidis3,2
  • Wei Guo3,4
  • Davy Deng5,2
  • Adam Amsterdam6,2
  • Lige Zhang1,2
  • Takato Honda3,4
  • Steven Roche3
  • Matthew A. Wilson3,4
  • Edward S. Boyden7,8,9,10,11,12,13
13 affiliations
  1. 1Department of Media Arts and Sciences, MIT, Cambridge, MA, USA
  2. 2McGovern Institute for Brain Research, MIT, Cambridge, MA, USA
  3. 3Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA
  4. 4Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA
  5. 5Harvard-MIT Health Sciences and Technology, Cambridge, MA, USA
  6. 6David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA
  7. 7Center for Neurobiological Engineering, Yang Tan Collective, and K. Lisa Yang Center for Bionics at MIT, Cambridge, MA, USA. [email protected]
  8. 8David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA. [email protected]
  9. 9Department of Biological Engineering, MIT, Cambridge, MA, USA. [email protected]
  10. 10Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA. [email protected]
  11. 11Department of Media Arts and Sciences, MIT, Cambridge, MA, USA. [email protected]
  12. 12McGovern Institute for Brain Research, MIT, Cambridge, MA, USA. [email protected]
  13. 13Mindspan Institute, Cambridge, MA, USA. [email protected]
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Abstract

Neurons interact in networks distributed throughout the brain. While much effort has focused on whole-brain calcium imaging, advances in genetically encoded voltage indicators raise the question of whether it might be possible to image neuronal voltage across entire brains. Achieving this requires a microscope with high volumetric imaging rates and signal-to-noise ratio. Here we present a remote-scanning light-sheet microscope capable of imaging genetically encoded voltage indicator-expressing neurons distributed throughout much of the brain of larval zebrafish at a volumetric rate of 200.8 Hz. We measured voltage traces from approximately one-quarter of all brain neurons. We found that neurons firing at different times during a sequence occupied different locations: visually evoked sequences mapped across the optic tectum, whereas stimulus-independent bursts were mapped across the cerebellum and medulla. Imaging voltage of neurons distributed in many brain regions may open new frontiers for understanding fundamental neural system operations.

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Cite

BibTeXRIS
BibTeX
@article{wang2026voltage,
  title = {{Voltage imaging of neurons distributed across entire brains of larval zebrafish}},
  author = {Zeguan Wang and Jie J. Zhang and Panagiotis Symvoulidis and Wei Guo and Davy Deng and Adam Amsterdam and Lige Zhang and Takato Honda and Steven Roche and Matthew A. Wilson and Edward S. Boyden},
  journal = {Nature Methods},
  year = {2026},
  month = aug,
  doi = {10.1038/s41592-026-03179-7},
  url = {https://doi.org/10.1038/s41592-026-03179-7},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Voltage imaging of neurons distributed across entire brains of larval zebrafish
AU  - Zeguan Wang
AU  - Jie J. Zhang
AU  - Panagiotis Symvoulidis
AU  - Wei Guo
AU  - Davy Deng
AU  - Adam Amsterdam
AU  - Lige Zhang
AU  - Takato Honda
AU  - Steven Roche
AU  - Matthew A. Wilson
AU  - Edward S. Boyden
PY  - 2026
DA  - 2026/08/14
JO  - Nature Methods
DO  - 10.1038/s41592-026-03179-7
UR  - https://doi.org/10.1038/s41592-026-03179-7
AB  - Neurons interact in networks distributed throughout the brain. While much effort has focused on whole-brain calcium imaging, advances in genetically encoded voltage indicators raise the question of whether it might be possible to image neuronal voltage across entire brains. Achieving this requires a microscope with high volumetric imaging rates and signal-to-noise ratio. Here we present a remote-scanning light-sheet microscope capable of imaging genetically encoded voltage indicator-expressing neurons distributed throughout much of the brain of larval zebrafish at a volumetric rate of 200.8 Hz. We measured voltage traces from approximately one-quarter of all brain neurons. We found that neurons firing at different times during a sequence occupied different locations: visually evoked sequences mapped across the optic tectum, whereas stimulus-independent bursts were mapped across the cerebellum and medulla. Imaging voltage of neurons distributed in many brain regions may open new frontiers for understanding fundamental neural system operations.
SN  - 1548-7091
SN  - 1548-7105
ER  -