Imagine being able to watch the brain’s inner workings in real time, like a live broadcast from the most complex organ in the body. But here’s where it gets controversial: what if we could do this without invasive procedures or damaging the very cells we’re studying? That’s exactly what a team of researchers has achieved by harnessing the power of light to measure activity in living brain cells—safely and effectively. A decade ago, a group of scientists had a literal lightbulb moment: they envisioned using bioluminescent light to illuminate brain activity from within. ‘What if we could light up the brain from the inside?’ wondered Christopher Moore, a professor of brain science at Brown University. This idea has now evolved into a groundbreaking tool that’s changing the game in neuroscience.
Traditional methods of measuring brain activity often rely on fluorescence, which involves shining external light onto the brain. While effective, this approach has drawbacks. And this is the part most people miss: prolonged exposure to high-intensity light can damage cells, and the molecules involved in fluorescence can degrade over time—a process called photobleaching. Additionally, the hardware required, such as lasers and fibers, makes the process more invasive. Moore and his team thought, ‘Why not use bioluminescence instead?’—a process where light is produced naturally within cells, eliminating the need for external illumination.
With a major grant from the National Science Foundation, the Bioluminescence Hub at Brown’s Carney Institute for Brain Science launched in 2017. Led by Moore, Diane Lipscombe, Ute Hochgeschwender, and Nathan Shaner, the team aimed to develop tools that give nervous system cells the ability to produce and respond to light. Their latest innovation, described in Nature Methods (https://doi.org/10.1038/s41592-025-02972-0), is the Ca2+ BioLuminescence Activity Monitor—or CaBLAM for short. This tool captures single-cell and subcellular activity at high speeds, works seamlessly in mice and zebrafish, and allows for multi-hour recordings without external light.
Here’s the bold part: CaBLAM is not just a tool; it’s a revolution in how we study the brain. ‘CaBLAM is a really amazing molecule that Nathan created,’ Moore says. ‘It lives up to its name.’ By avoiding the pitfalls of fluorescence, CaBLAM offers a safer, more sustainable way to monitor brain activity. But why is this so important? Measuring the ongoing activity of living brain cells is crucial for understanding how biological organisms function. While fluorescence has been the go-to method, its limitations have long been a stumbling block for researchers.
Bioluminescence, on the other hand, offers several advantages. Since it doesn’t rely on external light, there’s no risk of photobleaching or phototoxicity, making it safer for brain health. Plus, it’s easier to see. ‘Brain tissue already glows faintly when hit by external light, creating background noise,’ explains Shaner. ‘With bioluminescence, engineered neurons glow on their own, standing out against a dark background with almost no interference.’ It’s like giving brain cells their own headlights—you only need to watch the light coming out, even when scattered through tissue.
The concept of using bioluminescence to measure brain activity isn’t new, but making it bright enough for detailed imaging has been a challenge—until now. ‘These new molecules allow us to see single cells independently activated, almost like using a special, sensitive movie camera to record brain activity in real time,’ Moore says. CaBLAM can capture the behavior of a single neuron, even down to activity within sub-compartments of cells. In one study, the team recorded brain activity for five continuous hours—something impossible with fluorescence.
This breakthrough is part of a broader effort by the Bioluminescence Hub to control and observe brain activity in new ways. One project involves using living cells to send light signals to neighboring cells, effectively rewiring the brain with light. Another focuses on using calcium to control cellular activity. All these advancements hinge on brighter, better calcium sensors, which have become a key focus for the team.
Here’s where it gets even more exciting: Moore envisions CaBLAM being used beyond the brain, to study activity in other parts of the body. ‘This advance allows a whole new range of options for seeing how the brain and body work, including tracking activity in multiple parts of the body at once,’ he says. With contributions from at least 34 researchers across institutions like Brown, Central Michigan University, UC San Diego, UCLA, and NYU, this work is a testament to collaboration in science.
Funding for this research came from the National Institutes of Health, the National Science Foundation, and the Paul G. Allen Family Foundation. As we stand on the brink of this new era in neuroscience, one question remains: How will this technology reshape our understanding of the brain and beyond? What do you think? Is bioluminescence the future of brain imaging, or are there potential downsides we’re not yet considering? Share your thoughts in the comments!
Source: Brown University (https://www.brown.edu/news/2025-12-12/bioluminescence-brain-imaging-tool)
