This new imaging technology enables researchers to observe electrical activity in the brains of zebrafish on a millisecond timescale, potentially transforming our understanding of neural networks and behavior.
CAMBRIDGE, MA – Researchers at the Massachusetts Institute of Technology (MIT) have developed a groundbreaking microscope that allows for the imaging of electrical activity in the brains of zebrafish at a remarkable speed of 200 scans per second. This advancement, which was published in the journal Nature Methods, aims to enhance the understanding of how neurons interact within complex networks to control behaviors and brain functions.
Neurons communicate by generating electrical impulses that propagate through vast neural networks, crucial for functions like sensory perception, memory formation, and motor control. The new microscope offers a significant leap forward in neuroscientific research, as it enables real-time observation of these electrical activities across the entire brain of an organism.
Innovative Imaging Technique
The innovative technique employs genetically encoded voltage indicators—fluorescent proteins that light up when a neuron fires an electrical impulse. Previous imaging methods, such as calcium imaging, have been limited in speed, often taking seconds or minutes to capture neuronal activity, which is insufficient for observing rapid electrical spikes.
“Calcium imaging inherently is very slow, so you’re talking about imaging activity on the order of seconds or even minutes,” explained Jie Zhang, a lead author of the study and former postdoctoral fellow at MIT. “Typically that is too slow for us to be able to see a lot of these high-speed neural activities.” In contrast, the voltage imaging technique can provide direct observations of electrical activity, allowing researchers to track single spikes and rapid bursts of activity.
Enhancing the Light Sheet Microscope
The research team adapted a commonly used light sheet microscope, which illuminates thin sections of a sample using a sheet of laser light. By enhancing the speed of the microscope’s camera and employing a method called remote refocusing, they achieved the capability to scan the entire zebrafish brain at unprecedented speed.
“Different groups of neurons that are distributed across the brain coordinate together at millisecond timescales to generate a lot of behaviors and brain computations,” said Zeguan Wang, another lead author. “To understand the principles, we need the technology to observe their activity at the same time, across the whole brain, so we are not missing any important participant neurons.”
With this new capability, the researchers were able to image the brains of larval zebrafish, observing activity patterns in response to stimuli such as ultraviolet light. The initial tests revealed that while not every neuron expressed the voltage indicator, sufficient coverage was achieved to observe significant neural activity across the brain.
Future Implications for Neuroscience
The researchers noted that the ability to monitor how the brain activates in response to stimuli, such as the optic tectum’s response to visual input, opens new avenues for understanding brain function. The team observed that activity in the optic tectum propagated across different regions, highlighting the interconnectedness of neural networks.
Furthermore, the researchers aim to increase the percentage of neurons they can observe, enhance the microscope’s speed and resolution, and expand the technique’s application to other model organisms, including mice. This progress could provide neuroscientists with a powerful tool to formulate hypotheses about brain activity associated with various behaviors and cognitive states, potentially linking neural activity to complex phenomena such as daydreaming.
“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 stated, emphasizing the transformative potential of this technology.
Funding and Collaboration
The development of this technology was supported by a range of organizations, including the National Institutes of Health and the BRAIN Initiative, among others. The collaborative nature of the research included contributions from several postdoctoral researchers and graduate students affiliated with MIT’s McGovern Institute for Brain Research, the Yang Tan Collective, and the Koch Institute for Integrative Cancer Research.
As the field of neuroscience continues to evolve, this new imaging technology represents a significant step forward in the quest to decipher the complexities of the brain and its myriad functions.
For more information, refer to the original study: Wang, Z., et al. (2026). Voltage imaging of neurons distributed across entire brains of larval zebrafish. Nature Methods. DOI: 10.1038/s41592-026-03179-7.
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