Nobel Laureates Medicine 2014: Edvard & May-Britt Moser

On 6 October 2014, the Nobel Committee awarded Professors May-Britt and Edvard Moser the 2014 Nobel Prize in Physiology or Medicine. It was the first in this category for Norway. In videos taken that day, May-Britt Moser laughs, claps, and dances. Her husband [at the time of this interview, they announced their divorced 2016] and research partner Edvard Moser is not seen: he was on a plane to Munich when the announcement was made. When he landed, he said in an interview that day, “People came with flowers and I did not understand anything and then I found out because there were 150 emails and 75 text messages from the last 2 hours. And was one from [Nobel Committee for Physiology or Medicine Secretary] Göran Hansson.”

The Brain’s inner GPS

The Mosers, who met as University of Oslo students, have been faculty members at the Norwegian University of Science and Technology (NTNU) since 1996. Together, they ran the Centre for Neural Computation and the Kavli Institute for Systems Neuroscience in Trondheim. They shared the Nobel award with their mentor and colleague, Professor John O’Keefe from University College of London.

The honor is for work on what is being called the brain’s inner GPS, or global positioning system. This neural network provides the brain’s sense of place and internal map of the surroundings. The system tracks orientation and direction, with real-time updates for wayfinding.

In 1971, O’Keefe and colleagues first reported “place cells” in the hippocampus. The activation pattern of these cells reflects the external environment. Work in the early 2000s by the Mosers built on this discovery, adding information about distance and direction to this cognitive mapping system. The Mosers identified “grid cells” in the entorhinal cortex, which is next to the hippocampus and communicates with it. Like place cells, which fire in a pattern specific to the surroundings, grid cells are activated in a distinct pattern. The pattern is described as a hexagonal, beehive-like arrangement and changes with movement around an environment. Together, the place and grid cells create a network for spatial understanding. All these discoveries were made using electrodes that monitor brain cells in rats as they explore a space. Support for the same type of positioning system in humans comes from functional magnetic resonance imaging (fMRI) and brain cell recordings made during diagnosis and treatment of brain-related conditions.

Long-term research

In talking about their groundbreaking work, the Mosers graciously acknowledge coworkers, collaborators and funders. “One of the things that is unique in Norway,” said Edvard Moser, “is that the Research Council has a ten-year funding scheme. That allows us to plan for ten years of continuous science, to do long-term research, to set goals far ahead in the future and take risks.”

In addition to running a Centre of Excellence with funding from Norway, the Mosers directed a Kavli Institute. The Kavli Foundation, based in California, has established 17 institutes worldwide, to date. Potential sites undergo strict evaluation, but once they receive the Kavli Institute designation, funds can be used for whatever research the leaders feel is most important. “That means we can go in untraditional ways,” said Edvard Moser. “If we see something interesting, we can follow up on it.”

A major research center with a family feeling

Workplaces reflect the personalities and principles of their leaders and are shaped by the surroundings. Together, the Centre for Neural Computation and Kavli Institute for Systems Neuroscience are a well-funded, internationally respected research center in a city with fewer than 200,000 residents. This remarkable combination of global ambition and close-knit community echoes the determination of the Mosers and their long personal and professional relationship.

Jonathan J. Couey was a postdoctoral researcher at the Kavli Institute at NTNU in Professor Menno Witter’s group from 2008-2012. He was in 2014 a researcher in the Department of Psychiatry, Erasmus Medical Center, Rotterdam. A noteworthy feature of the Mosers’ work, said Couey, is that “most of their discoveries were made using a fairly simple recording technique. They just put animals in boxes and watch what their neurons do.” The work recognized by the Nobel committee, said Couey, didn’t require manipulations such as gene knockouts. “They can do extraordinary science on animals that are behaving normally, that are healthy and not in pain,” said Couey. “This means their science is technologically simpler and might even more accurately represent biological reality.” This type of science requires a particular skill, said Couey: “May-Britt and Edvard are extraordinarily good at making observations while asking clever questions.”

The Mosers have an infectious enthusiasm and their love of science is clear in online video interviews, even those taken before the Nobel Prize announcement. Couey confirmed this with a delightful story. While at the NTNU, he worked on an advanced in vitro brain-recording method complementary to the in vivo method used by the Mosers. “They’d never had anyone doing this before,” said Couey, “so Edvard said, ‘if you see anything, come and tell me.'” The first week, Couey had promising preliminary results, so he went to Edvard’s office to tell him. “He jumped out of his chair,” said Couey, “put on a lab suit, and came to watch the recordings himself. I knew then that he was just fascinated by the biology.”

The NTNU site is an exceptional place to work, Couey said, with state-of-the-art facilities. He was there at a time of extraordinary growth. “For a while,” he said, “we had group meetings with all the people from the institute in the same room. It was crowded but exciting.” Now, with seven active research groups, lab meetings are held separately. But the Mosers cultivated a work environment with a warm, family feeling, said Couey. “And of course, the science is incredible,” he said. “If you work hard, the Mosers work hard for you. They take care of the people from the institute.” Couey always felt that the Mosers would be given the Nobel Prize and is glad the honor has come relatively early in their career. “This is not a Nobel Prize that caps a career,” he said at the time of the announcement. “This will just make people more aware of their work.”

Opportunities ahead

The 2014 Nobel award added to the growing focus on brain research, which has seen enormous attention with the European Human Brain Project and the U.S. Brain Initiative. Neuroscience is trending, with opportunities for life scientists. “We’re focusing on basic research questions,” said Edvard Moser. “Once someone takes it further and applies it, for example to early Alzheimer’s disease, it will be interesting to the pharmaceutical industry, but we aren’t taking those steps. We’re simply trying to understand how the brain works.”

The life sciences industry supports neuroscience, including the study of neurological disorders, said Edvard Moser, through advances in methodology and instruments. “Neuroscience is undergoing tremendous development in technology,” said Edvard Moser. “We have technology that we couldn’t dream about 15 years ago such as optogenetics and pharmacogenetics. We can insert genes into specific classes of cells and use light or drugs to activate just those cell classes. Researchers now have a toolbox for selecting certain classes of cells, turning them on and finding out better how they work.” Using optogenetics, pharmacogenetics and optochemical genetics, brain researchers can use light, chemicals or both to selectively study particular brain cells. In addition, the Mosers and other brain researchers use electrophysiological recording equipment for monitoring brain cell signaling and the power and sophistication of these instruments is increasing. Edvard Moser advocated for making all these tools commonly and commercially available to everyone, not just the people who invent them and their collaborators. Said Moser, “It’s so important that industries that are participating in technological developments make new tools available to all researchers as soon as possible.”

A family endeavor

The Mosers are full partners in their research. “By and large,” said Edvard Moser, “we both cover the entire range of work. I travel a little more. Perhaps I do a little more writing papers and advising on analysis. Maybe May-Britt is more experimental, helping people do things in the lab. But our work is strongly overlapping.”

“We have the same vision. We love to understand and we do that by talking to each other,” said May-Britt in an interview the day of the Nobel Prize announcement.

In an annual tradition, all the 2014 Nobel Prize winners signed chairs on arriving in Stockholm for Nobel Week. With his signature, Edvard Moser wrote “Looking for crystals in the brain” and with hers, May-Britt Moser wrote “Passion for mysteries.”

May-Britt Moser

• Born: 1963, Fosnavåg, Norway
• Educated and trained: University of Oslo, University of Edinburgh, University College London
• Currently (2014): Director, Centre for Neural Computation, Norwegian University of Science and Technology