U OF M RESEARCHERS ARE DEMYSTIFYING OUR NERVE CENTER THANKS TO AN AWARD THAT ENCOURAGES THEM TO ASK “WHAT IF?”
A. David Redish is a neuroscientist, a teacher, and a Distinguished McKnight University Professor at the University of Minnesota. But there’s another title he prefers above all others: explorer.
“As researchers, we really are explorers,” Redish says. “If we knew what we were going to find, it wouldn’t be science.”
A desire to know the unknown is at the heart of any scientist’s pursuit. But the reality is that conducting research costs money. And finding funding to explore truly uncharted terrain is difficult, if not impossible. Major funders such as the National Institutes of Health (NIH) want to see that a project already shows promise before they’ll risk backing it. So how do researchers like Redish get their big ideas off the ground?
That’s where awards like those from the Winston and Maxine Wallin Neuroscience Discovery Fund come in. Established in 2011 with a gift from the former Medtronic CEO and his wife and supported annually by the Wallin family and other donors, the fund gives researchers with promising ideas the boost they need to move ahead with their work. “The Wallin Fund really gives us the opportunity to explore, go hunting, and get that evidence we need for further study,” Redish says. “It enables us to try crazy stuff.”
During the past nine years, the Wallin Fund has supported 38 research projects at the U. Altogether, those projects have gone on to receive an additional $19.2 million in outside funding. This effort to encourage innovative thinking has made the U a national leader in brain-related research and created a culture where scientists are encouraged to work together to pursue their most far-fetched ideas. “The spirit of the Wallin Fund is really to swing for the fences,” says Timothy Ebner, the U’s Max E. and Mary LaDue Pickworth Endowed Chair in Neuroscience and head of the U’s Department of Neuroscience.
FINE-TUNING EPILEPSY TREATMENT
Epilepsy is one of the most common neurological disorders, affecting nearly one in 26 people at some point in their life. Esther Krook-Magnuson, an assistant professor in the U’s Department of Neuroscience, is on a mission to help manage seizures caused by the disorder.
Although medication and surgery help some people, Krook-Magnuson says many are still unable to manage their seizures successfully, making everyday tasks almost impossible.
“Estimates show that up to half of patients with epilepsy don’t have their seizures controlled with current treatments. And even for those who do have their seizures under control, there can be severe side effects from treatment,” she says.
With support from a 2017 Wallin Fund award, Krook-Magnuson is focusing on temporal lobe seizures, a common type of seizure that starts in an area of the brain called the hippocampus. Using optogenetics, a technique that harnesses light to stimulate genetically modified neurons, Krook-Magnuson and her team learned that when they stimulated neurons in the cerebellums of mice, seizures in the hippocampus could be prevented. “That was surprising and exciting,” she says.
Although optogenetics is being used only in animal studies, Krook-Magnuson believes electrical stimulation, which can help people with Parkinson’s disease manage their pain and tremors, may offer similar benefits to those with epilepsy.
In her Wallin-funded project, Krook-Magnuson used information gleaned from her optogenetics work to explore whether the same principles applied when electrically stimulating parts of the cerebellum. After testing countless variables—stimulation location, frequency, duration, and intensity—Krook-Magnuson and her team found the “magic setting.”
“Knowing that allows us to move forward with the goal of actually using this tool to treat seizures and help those dealing with epilepsy,” she says.
Her lab is applying for additional funding from the NIH, something she said wouldn’t be possible without having done this study.
“Without the Wallin support, we’d still be wondering if electrical stimulation could work to treat seizures,” she says. “Now, we have good science to show to the NIH to say, ‘Hey, this is going to work.’”
Hear more from Esther Krook-Magnuson:
STOPPING RELAPSE BEFORE IT HAPPENS
Mark Thomas, a professor in the Department of Neuroscience and scientific director of the U’s Medical Discovery Team on Addiction, remembers the moment he became fascinated by the brain.
“It was my Biology 101 class, and the professor introduced us to the idea that, as we are experiencing the world, somehow some of that information is stored in our brains and impacts us for the rest of our lives,” he recalls. “I thought, ‘Wow, that’s amazing!’”
Thomas has since made brain research his life’s work. Specifically, he and his team are interested in how synapses—connections between brain cells—change when exposed to drugs.
“The challenge is figuring out which of those brain changes trigger behavior that can lead to compulsive drug seeking and drug use,” he says. “That’s what we’re after.”
Thomas is a two-time Wallin award winner. His first award in 2012 allowed him to study reward circuits that are activated during drug exposure and relapse. Using optogenetics in animal models to stimulate cells in the circuits affected by cocaine and amphetamines, he was able to reverse the negative effects of exposure and potentially prevent relapse.
The work allowed Thomas to secure external funding to look more closely at opioid addiction. He found optogenetics could be used to block opioid relapse in a similar fashion.
“We started thinking, ‘What’s the best way to translate this into something we could try with people?’” Thomas recalls. “That’s when the light went on that we could try brain imaging.”
Brain imaging tools such as magnetic resonance imaging (MRI) allow scientists to see inside the human brain, but they’re rarely used in animal models, Thomas says. What if they could identify the same drug-related synaptic changes in mice using MRI as they saw with optogenetics? That seemingly simple question led to Thomas’ second Wallin-funded project.
Working with colleagues at the U’s Center for Magnetic Resonance Research, Thomas was able to use MRI to successfully identify the same drug-related synaptic changes in rodents’ brains. It was a connect-the-dots moment linking his basic science findings to a clinical tool.
“This research could occupy a pivotal place in the trajectory of our work,” he says. “We now have some evidence that what we’re doing in animal models could work in humans dealing with drug addiction.”
Thomas and his colleagues are still combing through data from the MRI study, hoping to find further connections between drug exposure and changes happening across the brain’s trillions of synapses. It’s challenging work, he says, and it wouldn’t have been possible without support from the Wallin Fund.
“You want to go into unexplored territory, but sometimes that unexplored territory is kind of crazy. It could be a complete bust,” Thomas says. “With science, there’s not always a map to the treasure. The Wallin award allowed us to go searching.”
Hear more from Mark Thomas:
UNDERSTANDING THE BASIS OF DECISION-MAKING
A. David Redish’s research started with a straightforward idea: If we know how the brain processes information when it’s working well, then we can begin to understand what happens when things go awry, such as with psychiatric disorders.
“The brain is an information-processing machine,” he says. “So if we want to understand how it works, we have to understand how information is processed at the most basic level.”
That hypothesis was the driver behind Redish’s 2011 Wallin award. Using nanowire technology developed in his lab, Redish and his team recorded activity in individual brain cells in freely behaving rats—something that had never been done before. The recordings provided an unprecedented look inside the animal’s mind as it ran around and made choices.
That Wallin-funded project laid the groundwork for studies using innovative neuroscience technology in animals other than rats—including humans—which has put Redish and his colleagues “at the verge of an incredible breakthrough” in understanding how the brain processes information, he says.
He’s now working with colleagues across the U to translate those basic science breakthroughs into clinical solutions for anorexia, obsessive compulsive disorder, and other psychiatric disorders.
That collaborative spirit is something Redish says has been enhanced by the Wallin Fund. For the better part of a decade, the fund has encouraged researchers on campus to not only think about problem solving in a new way, but also explore creative partnerships.
“There was a feeling when the Wallin Fund started that this was going to launch neuroscience at the U into the stratosphere,” he says. “And that’s what has happened. It has made people think about things in a new light. It’s created a ‘We’re in this together’ mentality. People are noticing us. Minnesota is on the map in neuroscience.”
Justin Harris is a contributor to Legacy magazine.
Hear more from David Redish: