
High-speed microscopy reveals electrical activity across the brain
On Aug. 14, 2026, a team of engineers at Massachusetts Institute of Technology (MIT) announced they have invented a new microscope that can image electrical activity in neurons distributed across the brain of an entire organism, the experimental model Danio rerio (zebrafish).
Within the brain, neurons compute by generating electrical impulses. These signals travel throughout neurons, which are in turn connected in vast networks that control brain functions such as sensory perception, memory formation, and control of movement. This advance could help neuroscientists map those neural networks, leading to a better understanding of how neural activity underlies behavior and other brain functions.
Using a microscope that they adapted for fast, high-volumetric rate imaging, the researchers were able to track electrical activity across the brain on the scale of milliseconds. This method revealed patterns of neural activity from neurons throughout the brain that were activated in response to ultraviolet light. One technique often used to measure neuron activity in the brain is calcium imaging. Calcium flows into neurons after they fire an electrical impulse, so measuring calcium levels in the cells can serve as a proxy for neural activity. However, this type of imaging isn’t fast enough to capture single spikes of activity.
To enable direct imaging of voltage, researchers have developed proteins called genetically encoded voltage indicators — fluorescent proteins that can be genetically expressed in neurons. When a neuron fires an impulse, the protein fluoresces, which can be detected with a fluorescence microscope.
In previous work, researchers have used these proteins to image small populations of neurons, usually focusing on one localized part of the brain. Until now, there hasn’t been a way to image a large volume, such as the entire brain, with the millisecond-scale resolution needed to see electrical impulses from individual neurons.
To achieve that, the MIT team decided to modify a commonly used microscope known as a light sheet microscope. This type of microscope uses a sheet of laser light to illuminate a thin slice of a sample. By imaging many layers in sequence, this technique can generate 3D images of a large volume. However, with previous microscopes, the scanning of an entire volume would take too long to be able to capture neuronal impulses across the volume at single cell resolution.
To test the new microscope, the researchers engineered neurons in larval zebrafish to express a voltage indicator called Positron2-Kv. Although they had hoped that the indicator would end up in every neuron, it produced signals in neurons distributed throughout the brain, with about one quarter of the neurons exhibiting acceptable signals. This was enough, however, to observe patterns of activity across the brain. The researchers imaged the brain as the fish were resting, and they were able to observe single voltage spikes from neurons, as well as rapid bursts of spikes.
Additionally, this technique revealed patterns in how the brain is activated following a stimulus such as ultraviolet light. Immediately following the stimulus, activity was seen in the optic tectum, which receives and processes visual input from the retina. This activity propagated from one side of a part of the brain called the tectum to the other. Stimulus-independent activity also occurred in sequences across sets of neurons in the cerebellum and hindbrain.
The researchers now hope to increase the percentage of neurons that they can image across the brain, as well as the microscope’s speed and resolution. They are also working on expanding the use of this technique to other experimental models, including mice.
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Source: Massachusetts Institute of Technology
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