MIT researchers have built a microscope that images electrical impulses across the brain of a living zebrafish, capturing whole-organism neural firing at millisecond resolution.
The study, published August 14, 2026, in Nature Methods, describes a modified light sheet microscope capable of scanning an entire larval zebrafish brain 200 times per second, or once every five milliseconds.
Conventional neural imaging relies on measuring calcium levels inside cells. Calcium flows into neurons after they fire, but that process unfolds across seconds or minutes, making it too slow to detect individual electrical spikes. To observe voltage directly, the team engineered zebrafish neurons to express Positron2-Kv, a fluorescent protein indicator that illuminates when a cell fires an impulse.
MIT engineers increased the image acquisition speed of the microscope's camera and accelerated its volumetric scanning using remote refocusing. Standard light sheet systems scan too slowly to capture millisecond-scale electrical impulses across an entire organ. In testing, the modified setup recorded acceptable signals from approximately one-quarter of the neurons distributed across the zebrafish brain.
The microscope recorded single voltage spikes and rapid spike bursts while fish rested. When researchers presented an ultraviolet light stimulus, neural activity appeared immediately in the optic tectum and propagated from one side of the region to the other. Stimulus-independent firing sequences also occurred across groups of neurons in the cerebellum and hindbrain.
Senior author Ed Boyden and lead authors Zeguan Wang and Jie Zhang plan to expand the imaging technique to mice while working to increase the microscope's resolution, speed, and the percentage of active neurons it detects.
