Brain’s Positioning System Linked to Memory

The 2014 Nobel Prize in Physiology or Medicine was awarded to three researchers who discovered how the brain navigates the world. Their work may also help illuminate how the mind stores memories.

Google Maps, the powerful online mapping tool, owes its success to two key elements: GPS, which calculates a position on the Earth’s surface, and an exhaustive map that contains information such as your home address, your favorite restaurant, and the doughnut shop you pass on the way to work. It turns out that the brain’s navigational system works in much the same way. The three researchers responsible for this discovery have won the 2014 Nobel Prize in Physiology or Medicine.

The prize was jointly awarded to John O´Keefe, a neuroscientist at University College London, and May‐Britt and Edvard Moser, a married couple and neuroscience team at the Norwegian University of Science and Technology, for their research into how the brain navigates through space. In 1971, O’Keefe discovered special neurons called place cells, which fire whenever an animal is in a certain location. More recently, the Mosers identified grid cells, which are thought to act like a dead-reckoning system, telling the animal its location independent of external cues. Though first discovered in rats, both kinds of cells are widespread in mammalian brains, including those of humans.

One striking feature of this system of grid and place cells is that it seems to encode abstract properties. “The big breakthrough is that these cells are not just responding to sensory cues, like an odor on the ground,” said David Redish, a neuroscientist at the University of Minnesota in Minneapolis. Instead, grid cells form an internal positioning system, and place cells use that information along with other cues to create a sense of place. Together, they create a rich map. “Understanding how we build those maps is part of a larger framework of cognitive science — how do we build inner models?” said Matthew Wilson, a neuroscientist at the Massachusetts Institute of Technology.

A better understanding of the brain’s mapping technique may also lead to new insights in other areas of neuroscience. For example, “there is something fundamental about how we connect memory and space,” Wilson said. Rather than simply forming our inner GPS, place cells and grid cells may provide a system for anchoring our memories.

Sense of Place

Place cells are found in the hippocampus, which has long been considered the brain’s memory hub. Removing it, as happened with the famous patient H.M., wipes out the brain’s ability to form new memories. But O’Keefe’s discovery showed that the hippocampus is also essential for navigation.

O’Keefe recorded the impulses from neurons in a specific part of the hippocampus in rats as they explored an open space. He discovered that individual neurons would fire only when the rat was in a certain spot. By altering the surrounding environment, he showed that the animal wasn’t simply responding to sensory cues. Rather, the neurons were responding to a more sophisticated sense of location

In a seminal book published in 1978, O’Keefe and his co-author, Lynn Nadel, theorized that this spatial system might have a much broader role. Rather than simply providing a list of locations in a coordinate system, it might organize an individual’s memories according to where they occurred. “Place cells take the coordinate system and attach something to it,” Redish said. So when you sit at the kitchen table in your childhood home, you might remember your favorite apple pie from Thanksgivings past.

All hippocampal research since then has been in response to that book, whether an experiment agreed with or challenged the hypotheses it laid out, Redish said. “Either way, it changed everything.”

Dead Reckoning

Three decades later, the Mosers discovered a system of cells that are believed to provide spatial information to place cells. They probed individual neurons inside rats’ entorhinal cortex, an area of the brain that connects to the hippocampus. They then let the animals run around an empty space. Occasionally, the target neuron would fire. By mapping the points on the floor where this happened, the researchers discovered that the points where the neurons fired mapped out a grid of equilateral triangles. The arrangement was so well-defined that the researchers initially suspected an equipment malfunction.


“The fact they fired in this precise triangular arrangement was just unprecedented,” said Jim Knierim, a neuroscientist at Johns Hopkins University in Baltimore, Md. As soon as Knierim read the paper back in 2005, “I knew that it was going to be one of the most important findings in systems neuroscience,” he said. “Once the Mosers discovered grid cells” — the neurons that fired in the grid pattern — “we had a new handle on the GPS part of the [memory] system.” (While GPS is a convenient metaphor, scientists believe that grid cells actually use a dead-reckoning system to calculate location.)

Model of Efficiency

The hexagonal pattern of grid cell activity is repeated all over nature, from honeycombs to the benzene ring to a tightly packed crate of oranges. It’s a highly efficient arrangement; bees use hexagons in their combs to minimize their use of wax. In the grid-cell system, the hexagon isn’t a physical object. Rather, it’s the organization of space that encodes information most efficiently. “It’s the most efficient way to compress data,” said Marianne Hafting Fyhn, a neuroscientist at the University of Oslo in Norway and a former student of the Mosers. Researchers aren’t sure why grid cells use hexagons, but the hexagonal organizing principle has attracted attention from computational biologists, who are trying to figure out how the grid is generated.

One intriguing discovery is that grid cells can function in complete darkness, absent any visual cues. “This must reflect some internal brain dynamics that are in some sense independent of external sensory input,” Knierim said. “That’s one reason it’s so phenomenal — it gives us a window on understanding internal processing.”

Decoding the Brain

Scientists don’t yet know exactly how the mind constructs its spatial maps or how they are used for navigation. But the work of O’Keefe and the Mosers might ultimately illuminate much more than the brain’s navigational system. Researchers can easily measure neural activity and location in space, so neuroscientists are employing place cells and grid cells to study a variety of questions.

For example, researchers want to know more about how the brain encodes information about the world in electrical signals, and how it integrates new information as those signals move from region to region in the brain. “If we want to understand brain processing, we need to know what transformation occurs from one part of the brain to the next,” Knierim said. “What rules transform information from area A into information in area B?” The process by which grid cells send information to place cells in the hippocampus allows researchers to explore this question.

Scientists have also used place cells to learn more about memory. As a rat runs through a maze, a particular sequence of place cells fire. The sequence replays after the rat goes to sleep; researchers think that this replay helps to transfer the rat’s memory of the maze from the hippocampus into long-term storage.

More recent sleep studies suggest that the rat will replay the same pattern when it is in the maze again and needs to make a decision about where to go next. This may indicate that the rat is accessing memories of the maze as it mulls over the best path. “We know rats can do mental time travel,” Redish said, as they relive past events. “We are only able to know that because of place cells.”

Many researchers believe that memory and space are even more intricately linked. In a popular trick for remembering speeches, dating back to ancient Greece, the orator calls to mind a familiar path through a city and attaches a segment of the speech to each location along the path. This mnemonic may unwittingly exploit the fact that the hippocampus encodes both location information and autobiographical memories. “It just happens that space is a good way of organizing experiences,” Wilson said.

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