Fast volumetric imaging of a zebrafish seizure model with adaptive optics light sheet microscopy

Light sheet microscopy is a powerful tool for imaging live organisms. To enable high-speed volumetric imaging, we have developed a light sheet system incorporating an electrically tunable lens (ETL) capable of capturing volumes up to 499 × 499 × 150 μm³ at 4 volumes per second with near diffraction-limited resolution. The system employs sensorless adaptive optics to correct ETL induced system aberrations, extending the usable field of view by fivefold. We apply this system to image the propagation of seizures in zebrafish larvae and observe that seizures originate in the posterior brain, propagate anteriorly toward the optic tectum and gradually subside over tens of seconds.