MIT researchers have developed a method for imaging neuron activity in the zebrafish brain. Each colored spot (green and yellow) represents an active neuron. Credit: Courtesy of the researchers
MIT engineers have built a new microscope that can image electrical activity in neurons scattered throughout the entire brain of a living organism, capturing signals fast enough to catch individual nerve impulses.
For the study, published in Nature Methods, researchers adapted a light sheet microscope to scan the brain of larval zebrafish 200 times per second, or once every five milliseconds — fast enough to catch a neuron's electrical impulse as it happens rather than the slower chemical aftermath most current brain imaging methods rely on.
To make the neurons visible, the researchers engineered the fish to produce a light-up protein called Positron2-Kv that flashes each time a neuron fires. About a quarter of the brain's neurons produced usable signals, which was enough to reveal both single spikes and rapid bursts of activity while the fish rested quietly.
When the fish were exposed to ultraviolet light, the researchers watched activity spread through the optic tectum, the brain region that processes visual input, moving from one side of the structure to the other. Activity unrelated to the light stimulus also appeared in coordinated sequences across neurons in the cerebellum and hindbrain, hinting at ongoing background processing happening independent of outside stimuli.
Ed Boyden, professor of biological engineering at MIT and senior author of the study, said the technique addresses a fundamental gap in neuroscience, since brain regions don't work in isolation.
“A big question is simply to understand how neurons work together as a network, and this might be the first time that you could do that, because you can image the voltage of neurons distributed throughout the network,” Boyden said.
The researchers now plan to increase the share of neurons they can capture at once and push the microscope's speed and resolution further. They are also working to extend the technique beyond zebrafish to other animal models, including mice, with the eventual goal of helping neuroscientists generate new hypotheses about how brain-wide activity gives rise to behavior and mental states, such as daydreaming.
Data from MIT