Imaging the voltage of neurons distributed across entire brains of larval zebrafish

Zeguan Wang*, Jie Zhang*, Panagiotis Symvoulidis, Wei Guo, Lige Zhang, Matthew A. Wilson, Edward S. Boyden (2023) Imaging the voltage of neurons distributed across entire brains of larval zebrafish bioRxiv 2023.12.15.571964; doi: https://doi.org/10.1101/2023.12.15.571964 (*, co-first authors)

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Neurons interact in networks distributed throughout the brain. Although much effort has focused on whole-brain calcium imaging, recent advances in genetically encoded voltage indicators (GEVIs) raise the possibility of imaging voltage of neurons distributed across brains. To achieve this, a microscope must image at high volumetric rate and signal-to-noise ratio. We present a remote scanning light-sheet microscope capable of imaging GEVI-expressing neurons distributed throughout entire brains of larval zebrafish at a volumetric rate of 200.8 Hz. We measured voltage of ∼1/3 of the neurons of the brain, distributed throughout. We observed that neurons firing at different times during a sequence were located at different brain locations, for sequences elicited by a visual stimulus, which mapped onto locations throughout the optic tectum, as well as during stimulus-independent bursts, which mapped onto locations in the cerebellum and medulla. Whole-brain voltage imaging may open up frontiers in the fundamental operation of neural systems.

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Tools for recording brain signaling dynamics

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