A collaborative team of researchers, working across fields of study, has found a new way to control the conversation between any two cells by using a novel technology that replaces normal chemical brain communication with optical pulses.

Sensing touch, remembering a moment or solving a math problem all require brain cells to communicate in specific patterns, with a select group of cells in one brain area sending signals to distinct downstream groups in target brain areas. This precise communication cascade occurs by the release of chemicals, known as neurotransmitters, from the sending cell. These molecules then fit into a receptor in the target, like a puzzle piece finding its match, and change activity in the target. This chemical communication primarily occurs at points of contact called synapses.

Scientists have now created optical synapses by substituting optical communication for chemicals, using photons generated by activity in the sending cell to light up optical sensors in the target. The novel method is described in a study recently published in Communications Biology.

According to the researchers, this new method, and the unique specificity it provides, will allow a new regime of experiments for re-routing or changing information flow, and it may provide a unique approach to treating diseases that result from failed signaling in the brain.

“The brain makes behavior possible by changing its routing patterns, shifting to those appropriate to the moment,” said co-senior author Christopher Moore, professor of neuroscience at Brown University and associate director of the Carney Institute for Brain Science. “While we know that communication between specific sets of cells matters, exactly which cells and in which patterns are still great mysteries. This new approach gives us a powerful tool for selectively changing that conversation, letting us directly test a wide range of theories about how the brain talks to itself.”

The scientists achieved these light pulses by using bioluminescence in the senders, adapting the process that causes fireflies and jellyfish to glow. The receiving cells were made to express optical sensors, similar to the opsin molecules found in individuals’ eyes. This approach of expressing opsins in cells that don’t usually have them is known as optogenetics. Researchers can control precisely when the optical pathway is open because bioluminescence requires the presence of a small molecule not found in mammalian brains, Moore said. Together, these form the strategy of interluminescence, or light between cells.

"By doing this, researchers can more precisely control transmission of information between selected neurons by choosing pre- and postsynaptic partners, the time during which manipulation occurs, and the effects on the postsynaptic partner," said Ute Hochgeschwender, the study’s co-senior author and a professor of neuroscience at Central Michigan University.

While optical communication is already widely used in industry, such as in the fiber optics that transmit cable signals, this new optical synapses approach is the first to use light as a replacement technology for specific patterns of biological communication. 

Eureka moment

The idea behind this technology was set in motion almost exactly a decade ago, and it has required a team of researchers that transcends fields of studies—from molecular engineers to brain scientists.

When Moore and his colleagues came up with this novel way of changing how signals move through the brain, they didn’t have the ability to test it in their lab. Knocking on Diane Lipscombe’s door—the director of the Carney Institute, a professor of neuroscience at Brown and one of the study's co-senior authors—they explained the basics of the plan. 

“We had an awesome conversation and, literally within a week, we had the first evidence that bioluminescent light could drive optogenetics,” Moore said. “About a month later, we learned that Ute Hochgeschwender was already starting down this path, and she came and gave a really exciting talk at Brown. Soon after we all began collaborating. A big key to this progress was a Keck Foundation award, meant to spur progress in untested ideas, which allowed us to start working in earnest on this project.”

Robyn St. Laurent, a co-author of the recent study who was then a graduate student at Brown, came up with the key idea behind the molecular strategy for this approach. During an immersive eight-day workshop for Brown graduate students, St. Laurent was able to try the first version of her idea with help from Hochgeschwender and others. 

“The moment when we saw the cell culture flash brightly, everybody literally yelled,” Moore said. “It was that rare eureka, ‘wow this could work,’ kind of moment.”

The research team, which spans the country with labs at Brown, Central Michigan University and the University of California San Diego, was brought together by a grant from the National Science Foundation. The grant enabled the creation of the Bioluminescence Hub, which is dedicated to the development of novel bioluminescent and optogenetic tools and to the broad dissemination of those tools. National Institutes of Health funding was also crucial to these developments.

“It took a huge amount of creativity and hard work from Mansi Prakash, the first author of this study and a W. M. Keck postdoctoral fellow at Central Michigan University, to bring home the interluminescence concept,” Hochgeschwender said. “The study is an excellent example of productive collaboration combining talents with complementary expertise, scientific interest, ideas and intellectual synergism to reach a common goal.”

Treating diseases

Researchers say this novel approach of using bioluminescence to control communication between neurons can play a role in treating diseases. Changes in communication between cells—making these conversations too loud or too quiet—is a cause of several diseases, including epilepsy and Parkinson’s disease. 

“Optical synapses targeted to the specific circuits impacted in each disease, or in each individual, could be used as a therapeutic,” Moore said.

The technology has a variety of other benefits for research. A revolution in new methods has recently allowed scientists to control individual neurons in a given spot in the brain, but almost no technologies can selectively change the ongoing conversation between specific sets of cells in certain brain areas, according to the researchers. 

“It’s exciting to see optical synapses work,” Moore said. “It's a really wonderful example of collaboration across levels, labs and universities—team science really does work, and it often takes a team to make a clear piece of progress like this.”