A Sense of Where You Are: The way the brain records and remembers movement in space may be the basis of all memory

April 29, 2013

A Sense of Where You Are

The way the brain records and remembers movement in space may be the basis of all memory


TRONDHEIM, Norway — In 1988, two determined psychology students sat in the office of an internationally renowned neuroscientist in Oslo and explained to him why they had to study with him. Unfortunately, the researcher, Per Oskar Andersen, was hesitant, May-Britt Moser said as she and her husband, Edvard I. Moser, now themselves internationally recognized neuroscientists, recalled the conversation recently. He was researching physiology and they were interested in the intersection of behavior and physiology. But, she said, they wouldn’t take no for an answer. “We sat there for hours. He really couldn’t get us out of his office,” Dr. May-Britt Moser said. “Both of us come from nonacademic families and nonacademic places,” Edvard said. “The places where we grew up, there was no one with any university education, no one to ask. There was no recipe on how to do these things.” “And how to act politely,” May-Britt interjected. “It was just a way to get to the point where we wanted to be. But seen now, when I know the way people normally do it,” he said, smiling at the memory of his younger self, “I’m quite impressed.”

So, apparently, was Dr. Andersen. In the end, he yielded to the Mosers’ combination of furious curiosity and unwavering determination and took them on as graduate students. They have impressed more than a few people since. In 2005, they and their colleagues reported the discovery of cells in rats’ brains that function as a kind of built-in navigation system that is at the very heart of how animals know where they are, where they are going and where they have been. They called them grid cells.“I admire their work tremendously,” said Eric Kandel, the Nobel laureate neuroscientist who heads the Kavli Institute for Brain Science at Columbia and who has followed the Mosers’ careers since they were graduate students.

John O’Keefe of University College London, who in the 1970s identified the so-called place cells in the brain that register specific places, like the corner deli or grandma’s house, and who was one of the Mosers’ mentors, said that the discovery of the grid cells was “incredibly significant.”

The workings of the grid cells show that in the brain “you are constantly creating a map of the outside world,” said Cori Bargmann, of Rockefeller University, who is one of the two leaders of a committee set up to plan the National Institutes of Health’s contribution to President Obama’s recently announced neuroscience initiative.

Often, the workings of billions of neurons that produce our thoughts are opaque. But electrical recordings of signals emitted by grid cells show a map “with a framework and coordinates that are completely intuitive,” Dr. Bargmann said. And to find such a straightforward system is, in its own way, “just mind-boggling.” What is the brain doing being so mysteriously unmysterious?

The implications of the discovery are both practical and profound. The cells have been proved to exist in primates, and scientists think they will be found in all mammals, including humans. The area in the brain that contains the grid cell navigation system is often damaged early in Alzheimer’s disease, and one of the frequent early symptoms of Alzheimer’s patients is that they get lost. The Mosers do not work on humans, but any clues to understanding how memory and cognitive ability are lost are important.

On the most profound level, Dr. O’Keefe, the Mosers and others speculate that the way the brain records and remembers movement in space may be the basis of all memory. This idea resonates with the memory palaces of the Renaissance, imagined buildings that used spatial cues as memory aids. The technique dates to the ancient Greeks. In this regard, neuroscience may be catching up with intuition.

A Welcome Ambush

Edvard, 51, and May-Britt Moser, 50, now direct the Kavli Institute for Systems Neuroscience and the Centre for the Biology of Memory at the Norwegian University of Science and Technology here in Trondheim. They have a steady stream of findings coming from their lab, and a slew of awards, the latest of which, the Perl-U.N.C. Neuroscience Prize, they received April 16 at the University of North Carolina.

But they did not grow up in a center of academic ferment or intellectual competition. They were born and raised on islands off the coast of Norway a couple of hundred miles north of Bergen, part of an area known as Norway’s Bible Belt. They went to the same high school, but didn’t really get to know each other until they met again at the University of Oslo in the 1980s.

May-Britt, who grew up on a farm, remembers an environment in which drinking, card playing and dancing were all frowned upon. When she called home from Oslo announcing that she had been to a bar and had her first beer, her mother said, “And what’s next?”

The Mosers married in 1985 while still undergraduates. By the time they had finished their doctorates, in 1995, they had two daughters, but they were ready to see the world, to train in laboratories outside Norway. And they did spend time in England, with Dr. O’Keefe, and in Scotland, with Richard Morris at the University of Edinburgh.

But the Mosers’ travels were cut short when they were ambushed by a job offer too good to refuse, from the university in Trondheim, where they have been ever since.

“Without knowing it, we actually negotiated,” May-Britt said, “because we were not interested if we only got one job, and we got two jobs. And we were not interested if we did not get the equipment we needed, and they gave us that.” Suddenly, without having really planned it, they had their own lab.

Of course, nothing happens suddenly in research. They began in what Dr. May-Britt Moser described as a bomb shelter, and gradually, over time, built up their program. Similarly, they did not set out looking in the part of the brain where they ended up.

They began recording the activity of cells in the hippocampus, with electrodes implanted in the brains of rats as they roamed an enclosed area. This is still a main method, and the rats are intriguing to watch, pursuing little bits of chocolate cereal on the floor of an enclosure, seemingly oblivious to the implants attached to their skulls.

A Black Box

The Mosers wanted to find how information was flowing to the place cells, whether it was going from one area of the hippocampus to another. But even after they inactivated sections of this brain area, the place cells still functioned. So it seemed that information was flowing in from the nearby brain area, the entorhinal cortex.

They started looking there, and in their early work they were helped by Menno Witter, then in Amsterdam, now at Trondheim, in the delicate task of guiding the electrodes to the right spot.

“We didn’t immediately find the grid cells,” Dr. Edvard Moser said. At first they noticed cells that would emit a signal every time a rat went to a particular spot, and they thought that perhaps this was something like the place cells in the hippocampus that are tied to locations in the outside world. But gradually they learned that what they were seeing was a cell that tracked the rat’s movement in the same way, no matter where the rat was. The cell was not responding to some external mark, it was keeping track of how the rat moved. And when they gave the rats enough room, a very regular pattern emerged.

“The first thing was that we thought there was something wrong with the equipment,” Dr. Edvard Moser said.

“I thought, ‘Is this a bug?’ ” Dr. May-Britt Moser said.

After a 2005 paper in Nature, in which they reported the discovery and named the cells, other labs confirmed the findings and more discoveries followed, in their lab and elsewhere.

It is now clear that the grid cells, in combination with cells that sense head direction and others that sense borders or boundaries — both originally identified in other parts of the brain by other labs — form a kind of dead-reckoning navigation system in the brain that maps movement.

Information flows from this part of the brain to the hippocampus, and then back. Exactly how the grid informs the place cells, and vice versa, is not known.

What scientists have now are two ends of a system with a black box in the middle that is not fully understood. At one end are place cells. At the other are grid cells. As to what exactly happens in between, and how the grid cells form in the first place, Dr. Edvard Moser said, “That’s still a 10-, a 20-year research problem.”

Or, as Dr. O’Keefe put it, “We are still in the pre-Newtonian phase of neuroscience.”

The Mosers remain something of an anomaly. Not only are they off the beaten academic track, but they are a married couple who work together on the same scientific problems at the same institution at the highest levels of science, a true rarity.

They do have different spheres in their new, state-of-the-art lab. May-Britt is more hands-on with the experiments and the design, and Edvard is more involved in mathematical analysis and interpretation of the results.

“We have a common project and a common goal,” he wrote in response to an e-mailed question, “and we both intensely burn for it. And we depend on each other for succeeding.”

He continued, “Most couples manage to cooperate on child raising — for us, our brain project is our third child, so nothing different, really.”

About bambooinnovator
Kee Koon Boon (“KB”) is the co-founder and director of HERO Investment Management which provides specialized fund management and investment advisory services to the ARCHEA Asia HERO Innovators Fund (www.heroinnovator.com), the only Asian SMID-cap tech-focused fund in the industry. KB is an internationally featured investor rooted in the principles of value investing for over a decade as a fund manager and analyst in the Asian capital markets who started his career at a boutique hedge fund in Singapore where he was with the firm since 2002 and was also part of the core investment committee in significantly outperforming the index in the 10-year-plus-old flagship Asian fund. He was also the portfolio manager for Asia-Pacific equities at Korea’s largest mutual fund company. Prior to setting up the H.E.R.O. Innovators Fund, KB was the Chief Investment Officer & CEO of a Singapore Registered Fund Management Company (RFMC) where he is responsible for listed Asian equity investments. KB had taught accounting at the Singapore Management University (SMU) as a faculty member and also pioneered the 15-week course on Accounting Fraud in Asia as an official module at SMU. KB remains grateful and honored to be invited by Singapore’s financial regulator Monetary Authority of Singapore (MAS) to present to their top management team about implementing a world’s first fact-based forward-looking fraud detection framework to bring about benefits for the capital markets in Singapore and for the public and investment community. KB also served the community in sharing his insights in writing articles about value investing and corporate governance in the media that include Business Times, Straits Times, Jakarta Post, Manual of Ideas, Investopedia, TedXWallStreet. He had also presented in top investment, banking and finance conferences in America, Italy, Sydney, Cape Town, HK, China. He has trained CEOs, entrepreneurs, CFOs, management executives in business strategy & business model innovation in Singapore, HK and China.

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