Neuroscience: Brains of Norway
Nobel prizewinners May-Britt Moser and Edvard Moser have spent a career together near the Arctic Circle exploring how our brains know where we are.06 October 2014
In the 1970s, O’Keefe had discovered neurons called place cells in the hippocampi of rats. These cells fire only when an animal is in a particular place — close to an exercise wheel, for example, or in front of a door. (Since then, other navigation-related neurons have been discovered, including those that fire when the head turns in a particular direction, or when a border, such as the long edge of a cage, is in view.) The research area was red hot, and the Mosers wanted to extend it.
But in 1996, just a few months into their postdocs, the Mosers received a surprise offer of two associate professorships at the Norwegian University of Science and Technology in Trondheim. They weren’t sure about accepting: it would mean striking out alone, in a small university in a country isolated from the world’s major centres of research. “But the offer of two posts in the same place and in the same research area was too good to turn down,” Edvard says. They flew back home, by this time trailing a toddler and baby.
The researchers saw that some of these entorhinal neurons fired when the rats moved onto or through a particular spot in the box, just like hippocampal place cells. But they went on to fire at several other spots too. While a rat scurried around mopping up chocolate treats, the researchers watched, perplexed, as the computer mapped the firings, and overlapping blobs appeared on the screen. The Mosers could see that the blobs were creating some sort of pattern, but they couldn’t work out what it was.
It took some months before it dawned on them that they needed the rats to run around bigger boxes, so that the pattern would be stretched out and easier to see. At that point, it came into view: a near-perfect hexagon lattice, like a honeycomb. At first they refused to believe it. Such simplicity and regularity was the last thing they had expected — biology is usually a lot messier than this. But one by one, the pair ruled out all other explanations — that the pattern was an artefact from their electronic equipment, for example — and then they began to understand how this part of the brain was working. There were no physical hexagons traced on the floor; the shapes were abstractly created in the rat’s brain and imposed on its environment, such that a single neuron fired whenever it crossed one of the points of the hexagon. The discovery was exciting for more than its pleasing pattern. This representation of space in brain-language was one of the long-sought codes by which the brain represents the world around us. “It was a long-drawn-out eureka moment,” recalls Edvard. The team published the discovery in Nature3 in 2005.
Soon the Mosers were putting the grid cells to the test. They showed that the firing pattern of the cells remained constant even in the dark, and that they are independent of the animals’ speed or direction3. Whereas place cells in a rat brain may change their firing rates if their environment is altered even a little — for example by changing the colour of the walls — those of grid cells remain robustly unchanged. The Mosers also found that the different cells in the entorhinal cortex generate grids of many different types, like overlapping honeycombs — big, small and in every orientation and position relative to the box’s border. And they ultimately came to see that the brain’s grid cells are arranged according to a precise mathematical rule.
The cells that generate smaller grids, with narrower spacing, are at the top of the entorhinal cortex, and those that generate bigger grids are at the bottom. But it is even more exact than that: cells that make grids of the same size and orientation seem to cluster into modules. The modules are arranged in steps down the length of the entorhinal cortex, and the size of the grid represented by each module expands by a constant factor of 1.4 with every step4. At the same time, grid cells that represent different positions relative to the box’s border are dotted randomly through the structure. Assuming a similar arrangement exists in humans, the idea is that, together, these cells are unconsciously keeping track of where we are as we wander between rooms or stroll down a street.
Also at Science News:
Three researchers honored for pinpointing how brain orients itself in space
O’Keefe: David Bishop/UCL; M.-B. and E. Moser: Geir Mogen/Kavli Institute for Systems Neuroscienc
Mapping the brain’s GPS system has earned three neuroscientists the 2014 Nobel Prize in physiology or medicine. John O’Keefe of University College London shares the prize with husband-and-wife duo May-Britt Moser and Edvard Moser of the Norwegian University of Science and Technology in Trondheim.
By discovering nerve cells that a rat uses to keep track of its location, the scientists offer a strikingly clear example of how the brain makes sense of its environment. The discovery of these navigational cells “is one of the most exciting stories in brain and cognitive sciences today,” says cognitive scientist Barbara Landau of Johns Hopkins University.
O’Keefe’s and the Mosers’ work both relied on some of the best navigators around — rats. In 1971, O’Keefe found that certain cells in the rat hippocampus, a brain region involved in memory, became active only when the animal was in particular spots. These “place cells” allowed an animal to form an internal map of its surroundings. Unlike many earlier experiments, O’Keefe’s work studied animals as they moved freely about an area. O’Keefe, who will receive half of the roughly $1.1 million prize, used implanted electrodes to record the behavior of neurons in the rats.
More than three decades later, the Mosers discovered what they dubbed “grid cells” in a nearby brain area, the entorhinal cortex. These cells fired off signals when a rat passed through certain locations spaced at regular intervals, becoming active in multiple locales that correspond to a grid similar to a Chinese checkerboard or hexagonal beeswax.
Along with other cells that take note of a rat’s head position and a location’s borders, grid cells send messages to place cells in the hippocampus, the Mosers found. The resulting elaborate network of neurons allows an animal to know where it is in the world.
This work is important not just because of what it reveals about how rats find their way through space, says cognitive neuroscientist Russell Epstein of the University of Pennsylvania. “It’s one of the best examples we have of how information can be encoded in the nervous system.”
Such cells are present in people, too. With implanted electrodes, scientists uncovered place cells in the brains of people in 2003 and grid cells in 2013 (SN Online: 8/5/13). “From what we can tell, there’s quite a bit of similarity between rats and people,” says neuroscientist Joshua Jacobs of Drexel University, who helped find grid cells in people.