Montana State University

MSU researchers’ tools for studying the brain being used worldwide

April 27, 2016 -- By Marshall Swearingen for the MSU News Service

MSU professor Thom Hughes, left, research professor Mikhail Drobizhev and Ph.D. student Lauren Barnett study a petri dish containing proteins in Hughes' laboratory in Bozeman. These proteins, which cause jellyfish to glow, are part of biotechnology that will allow researchers to study brain function with greater fidelity. MSU photo by Kelly Gorham.A filter and ultraviolet light reveals proteins known to cause jellyfish to glow. These proteins are part of biotechnology that will allow researchers to study brain function with greater fidelity. MSU photo by Kelly Gorham.

MSU professor Thom Hughes, left, research professor Mikhail Drobizhev and Ph.D. student Lauren Barnett study a petri dish containing proteins in Hughes' laboratory in Bozeman. These proteins, which cause jellyfish to glow, are part of biotechnology that will allow researchers to study brain function with greater fidelity. MSU photo by Kelly Gorham.

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BOZEMAN – A Montana State University researcher is part of a team that has published findings on the development of an improved tool for understanding the workings of the brain.

The tool, called genetically encoded voltage indicators, or GEVIs, is a biotechnology that enables researchers to see the electrical activity of individual neural cells “light up” when active.

“Imagine staring at a living brain and watching the billions of cells within it twinkling like stars as they talk with one another. This has been the dream of neuroscientists for many years,” said Thom Hughes, a professor in MSU's Department of Cell Biology and Neuroscience in the College of Letters and Science.

This dream of watching the cells of the brain is close to being realized through the concerted efforts of neuroscience laboratories across the world, of which MSU is a part, said Hughes.

The technology has the potential to allow researchers to study brain function with far greater fidelity than other technologies such as functional MRI, which detects changes in blood flow.

Hughes, along with colleagues at the Yale University School of Medicine and Korea Institute of Science and Technology, summarize recent advances in GEVIs in an article published in the April issue of the journal “Trends in Neurosciences.” The article, "Toward better genetically encoded sensors of membrane potential," appeared online April 26.

While functional MRI and other technologies have led to an understanding of which parts of the brain correspond to certain behaviors and thought processes, the working of the brain's billions of neurons — tiny, interconnected cells that transmit information through electrical and chemical signals — remains largely a mystery.

"Functional MRI is like asking, 'Is the action in New York or Boston?’” said Hughes. With GEVIs, "we're asking about the actual intersections and streets." 

GEVIs are made by fusing the genes that cause fluorescence from jelly fish and other sea creatures to the genes encoding voltage-sensitive proteins.  The final product, a synthetic fusion gene, can then be introduced into neurons through a virus, or stably inserted into the genome of a mouse or rat. The results are nerve cells that flash when the cells are involved in a thought.

Hughes's Molecular Motion Lab at MSU has been working since 1993 in the field and has pioneered the production of the new generation of GEVIs described in the Trends in Neurosciences’ article.  The GEVIs Hughes’ lab produces for research at Yale University School of Medicine and other universities is helping advance brain research around the globe.

“Making these genes is not trivial; it involves a great deal of synthetic DNA work, which is what my lab does, coupled with extensive testing in many different kinds of neurons,” Hughes said.

“The work begins here in Bozeman, where the team builds new genes. The DNA is then shipped to laboratories all over the world that test the resulting protein sensors in many different kinds of cells. Video conferencing with sites in South Korea, Japan, Washington D.C. and Paris makes it possible to share results quickly, redesign promising prototypes, and then my lab goes back to work making the next generation,” Hughes said.

Another important advancement of the group has been the development of specialized optics, typically inserted into the brain using tiny probes, to observe in real-time how a small set of neurons light up when a rat navigates a maze, for example.

"We're slowly getting bigger and brighter signals," said Hughes.

Hughes and his international research team hope to soon use GEVIs to simultaneously record thousands of neuron interactions during complex behavior or thought.

Hughes's team is supported in part by the National Institutes of Health’s BRAIN Initiative, a public-private collaborative announced by President Barack Obama in 2013 that includes scientists from across North America, Europe, Asia and the Middle East. U.S. universities involved include Harvard, Caltech, MIT, Stanford, Columbia and MSU.  

The BRAIN Initiative has channeled substantial funding from private foundations and federal agencies, including the National Science Foundation, toward its stated goal of "revolutionizing our understanding of the human brain."

"Professor Hughes's group of colleagues and collaborators is one of the leading groups in the world for developing genetically encoded sensors," said Frances Lefcort, head of the MSU Department of Cell Biology and Neuroscience.

Lefcort added that another MSU neuroscience professor, Charles Gray, has also received a prestigious BRAIN Initiative grant for similar research. And she noted that MSU physics professor Mikhail Drobizhev has also played a key role by developing the optical imaging used with GEVIs.

"My generation was raised thinking that we could never really understand how the circuits in the brain work, that the problem was just too hard,” Hughes said. “Now we're at a really special moment in history, because we actually have the tools and the willpower to try."

Contact: Thomas Hughes, (406) 994-5395 or thughes@montana.edu