MIT develops whole-brain voltage imaging microscope

MIT engineers have developed a new microscope that can image electrical activity in neurons distributed across the entire brain of a living organism at millisecond-scale speeds. The system, demonstrated in larval zebrafish, captures voltage changes from individual neurons throughout the brain rather than focusing on a small, localized region. The advance could give neuroscientists a new way to study how distant brain areas coordinate their activity to produce perception, movement, memory, and behavior. The work, published in Nature Methods, addresses a longstanding challenge in neuroscience: observing fast electrical signals across a large volume of brain tissue at the same time. The researchers modified a light-sheet microscope, increasing camera acquisition speed and using remote refocusing to scan the entire zebrafish brain 200 times per second. They engineered neurons to express a genetically encoded voltage indicator called Positron2-Kv, and observed single voltage spikes and rapid bursts of activity in resting fish. When exposed to ultraviolet light, activity spread through the optic tectum, and stimulus-independent sequences were seen in the cerebellum and hindbrain. The team plans to increase the proportion of neurons imaged, improve speed and resolution, and extend the technique to mice. The research was funded by the United States — National Institutes of Health, the United States — NIH BRAIN Initiative, the Picower Institute Innovation Fund, and the Howard Hughes Medical Institute, among others.