Researchers have developed a new bioluminescent imaging tool that allows neurons to glow from within, enabling real-time observation of brain activity without external lasers. This innovation, called CaBLAM, overcomes limitations of traditional fluorescence methods by providing clearer, longer-lasting recordings in living animals. The tool promises deeper insights into neural function and potential applications beyond the brain.
About a decade ago, scientists at Brown University began exploring the concept of illuminating the brain from the inside using bioluminescence. This idea led to the establishment of the Bioluminescence Hub in 2017 at the Carney Institute for Brain Science, funded by a National Science Foundation grant. The hub united experts including Christopher Moore, an associate director at the institute; Diane Lipscombe, the director; Ute Hochgeschwender from Central Michigan University; and Nathan Shaner from the University of California San Diego.
The team's breakthrough is the Ca2+ BioLuminescence Activity Monitor, or CaBLAM, detailed in a 2025 Nature Methods study. Shaner led the design of its core molecule, which enables high-speed capture of activity in individual cells or subregions without any external light. It has been tested effectively in mice and zebrafish, supporting recordings up to five hours long.
"We started thinking: 'What if we could light up the brain from the inside?'" Moore explained, highlighting the shift from fluorescence techniques that require lasers and risk damaging cells through photobleaching or phototoxicity. In contrast, bioluminescence generates light internally via an enzyme reaction, avoiding background noise from tissue scattering and producing sharper images.
"Brain tissue already glows faintly on its own when hit by external light, creating background noise," Shaner noted. "The brain does not naturally produce bioluminescence, so when engineered neurons glow on their own, they stand out against a dark background."
This advance allows observation of single neurons firing in living animals, crucial for studying complex behaviors and learning. Moore emphasized its potential: "These new molecules have provided, for the first time, the ability to see single cells independently activated, almost as if you're using a very special, sensitive movie camera."
The project involved 34 scientists from institutions like Brown, UCLA, and NYU, supported by the National Institutes of Health, NSF, and the Paul G. Allen Family Foundation. Beyond neuroscience, CaBLAM could track activity across the body simultaneously, expanding research possibilities.