Scientists Illuminate Brain Activity with Revolutionary Bioluminescence Tool, ‘CaBLAM’
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A groundbreaking new technique allows researchers to safely and effectively measure activity in living brain cells using light produced from within the cells themselves, offering a significant advancement over traditional methods.
For decades, scientists have sought a less invasive and more accurate way to visualize the intricate workings of the brain. Now, a collaborative team led by researchers at Brown University has developed a tool called the Ca2+ BioLuminescence Activity Monitor – or “CaBLAM” – that promises to revolutionize neuroscience.
The Challenge with Traditional Brain Activity Measurement
Current methods for measuring brain activity often rely on fluorescence, a process that involves shining light on the brain and detecting the emitted light. While useful, this approach has limitations. As one researcher explained, “Shining light on the brain is used to measure activity…But shooting lasers at the brain has downsides when it comes to experiments, often requiring fancy hardware and a lower rate of success.” These downsides include potential damage to cells from prolonged light exposure, a phenomenon known as photobleaching where the fluorescent molecules lose their ability to emit light, and the need for invasive hardware like lasers and fiber optics.
Bioluminescence: Lighting Up the Brain From Within
The team hypothesized that harnessing bioluminescence – light produced by living organisms – could overcome these challenges. Bioluminescence occurs when an enzyme breaks down a specific molecule, creating light without the need for external excitation. “We started thinking: ‘What if we could light up the brain from the inside?’” said a professor of brain science at Brown University.
In 2017, the Bioluminescence Hub at Brown’s Carney Institute for Brain Science was launched with a major grant from the National Science Foundation, fostering collaboration between researchers at Brown University, Central Michigan University, the University of California, San Diego, and others. Their goal: to develop and refine neuroscience tools based on bioluminescence.
Introducing CaBLAM: A New Era of Brain Imaging
The culmination of this effort is CaBLAM, described in a recent study published in Nature Methods. This innovative tool captures single-cell and subcellular activity at high speeds, functioning effectively in both mice and zebrafish. Crucially, CaBLAM eliminates the need for external light, enabling multi-hour recordings previously impossible with fluorescence-based methods.
According to researchers, CaBLAM is a remarkable molecular creation. “CaBLAM is a really amazing molecule that Nathan created,” a researcher stated, “It lives up to its name.” The tool’s ability to capture detailed brain cell activity stems from its sensitivity and the clarity it provides. “The brain does not naturally produce bioluminescence, so when engineered neurons glow on their own, they stand out against a dark background with almost no interference,” explained a researcher at UC San Diego. “And with bioluminescence, the brain cells act like their own headlights: You only have to watch the light coming out, which is much easier to see even when scattered through tissue.”
Beyond Single-Cell Resolution: Long-Duration Recordings and Future Applications
CaBLAM’s capabilities extend beyond simply detecting activity; it can capture the behavior of individual neurons and even activity within specific compartments of those cells. The team demonstrated this with a recording session lasting five continuous hours – a feat unattainable with traditional fluorescence techniques. “For studying complex behavior or learning, bioluminescence allows one to capture the entire process, with less hardware involved,” a researcher noted.
This breakthrough is part of a larger initiative to develop new methods for controlling and observing brain activity. Current projects include exploring how to use light to facilitate communication between neurons – effectively “rewiring the brain with light” – and engineering methods to control cellular activity using calcium. These endeavors all rely on increasingly sensitive and reliable calcium sensors, which have become a central focus of the hub’s research.
Looking ahead, researchers envision CaBLAM’s application extending beyond the brain. “This advance allows a whole new range of options for seeing how the brain and body work,” a researcher said, “including tracking activity in multiple parts of the body at once.”
The project involved contributions from at least 34 researchers across multiple institutions, including Brown University, Central Michigan University, UC San Diego, the University of California Los Angeles, and New York University. Funding for the research was provided by the National Institutes of Health, the National Science Foundation, and the Paul G. Allen Family Foundation.
