(Bloomberg) — The video starts with the image of a ghostly gray neuron. A flash of red flickers in one of the brain cell’s arms, vanishes, then comes back, flowing down the tendril to the heart of the cell and flooding it with color.
The footage captures a neuron firing, letting researchers watch the signal flowing through an entire cell for the first time. Seeing these cells at work may let researchers track and measure brain activity, including firing patterns of cells affected by disorders like epilepsy or multiple sclerosis.
The video, published online in the journal Nature Methods in June, shows a new method for converting electrical activity into fluorescent light. This nascent technology was discovered by 35-year-old Harvard University neuroscientist Adam Cohen, a native New Yorker with two doctorates under his belt. Pharmaceutical companies from Biogen Idec Inc. to GlaxoSmithKline Plc have already lined up to collaborate with Cohen’s biotechnology firm, Q-State Biosciences, hoping to advance drug development.
“Getting a good voltage sensor has been a holy grail in the field for 40 years,” said Michael Hausser, a neuroscientist at University College London who wasn’t involved in Cohen’s project. “The signals are the language of the brain — if you have a good sensor, it opens up a whole world of different experiments and potentially new therapies.”
Cohen’s work is based on a single-celled organism from the Dead Sea, Halorubrum sodomense, which has a protein that converts light into energy. While similar proteins had been used by other researchers to stimulate mice brains with light, Cohen had a different idea: Could he run the protein in reverse, so it would sense electricity and turn it into light?
If his idea worked, researchers might be able to visualize electrical activity in neurons, the cells that are key components of the brain, spinal cord and central nervous system.
For decades, scientists have struggled to find a way to monitor neural conversations, stymied by the complexity and the delicate nature of the brain, which makes it difficult to access.
Daniel Hochbaum, a postdoctoral fellow in Cohen’s lab, likens a neuron to a meatball with spaghetti strands. With current technology, scientists can track electrical activity only in the heart of the neuron — the meatball — by carefully inserting probes or injecting dyes with tiny glass pipettes, a process that is slow and delicate and only lets researchers track one cell at a time.
One other way currently used to monitor brain cell activity is via calcium imaging, since calcium concentration is affected when neurons fire. However, this is an indirect way of reading activity.
“There really are no other alternatives to studying the individual cells,” Hochbaum said by phone. “You’re not going to scoop them out of a live human’s brain.”
With Cohen’s proteins, however, voltage changes are tracked through the entire neuron, even down to the tiny arms — the spaghetti strands — that probes can’t penetrate. It’s also more efficient: under a microscope, Cohen’s lab can watch dozens of neurons in a petri dish fire in concert.
In short, “you can throw away the electrodes,” said Hausser.
Cohen first had the idea to reverse-engineer the light-sensitive proteins in 2009, but tried and failed with more than 40 candidates. Hochbaum spent about a year toiling over a single protein that worked in bacteria but refused to comply in a mammalian cell.
After coming across Halorubrum sodomense in an academic paper on another topic, the researchers gave it a try — and it worked right away. Hochbaum vividly remembers his first time watching the recording. When he started to see the fluorescence fluctuate in sync with the voltage, he jumped out of his seat. “I was dancing everywhere,” he said.
When he showed Cohen the data, however, they were mystified to see that halfway through the recording, the signals started degrading. They couldn’t figure out what was causing the recording quality to drop, so they ran the trial again.