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Understanding the brain’s GPS: how a Nobel Prize was just the beginning

When you decide to go from A to B, your brain’s own equivalent of GPS takes care of the task. How this system works has been revealed over the last few decades, leading to the award of a Nobel Prize in 2014.

But the story is far from over. This year, scientists have published research that not only sheds new light on navigation but could possibly lead to better treatments for disorders like Alzheimer’s.

The first breakthrough came in 1971, when John O’Keefe studied rats moving around a box. By attaching electrodes to a region of the brain called the hippocampus - a region of the brain associated with memory - O’Keefe showed that certain nerve cells were always active when the rat was in a particular place. By firing in different combinations, these ‘place cells’ mapped the environment.

A similar mechanism is at work in other animals, including humans. And in the rare cases where electrodes have been implanted in human brains, such as in patients with epilepsy, nerve cells that operate like the rats’ place cells have been found.


14599057004_9dc53af6f9_z image credit: aboutmodafinal.com


So how do they work? “Each cell represents many places,” explains Dr Hugo Spiers, who leads the UCL Spatial Cognition Group at University College London. “One might like your desk chair but maybe also gets excited in the middle of a park. Another cell perhaps doesn’t like that park but does like your desk chair. When those two cells are on together, the rest of your brain knows you’re in your desk chair,” he says.

The second big breakthrough in understanding animal navigation came in 2005. In Norway, the husband-and-wife team of May-Britt and Edvard Moser followed up O’Keefe’s discovery on place cells with more rat studies. They found that cells in a different part of the brain - the entorhinal cortex - were active when rats passed certain locations.

These locations formed a hexagonal grid, suggesting that this was the rats’ very own coordinate system. The cells were dubbed ‘grid cells’ and the discovery gave the Mosers one-half of the 2014 Nobel Prize in Physiology or Medicine. The other half was awarded to the 74-year-old Prof John O’Keefe, by now the director of the Sainsbury Wellcome Centre at University College London.

In addition to place cells and grid cells, there’s a third set called ‘head direction cells’. An individual head cell fires more often when an animal’s head is pointing in a particular direction. This helps us navigate by acting like a compass. The difference is that head direction cells are guided not by the Earth’s magnetic field but the vestibular system in the ear, which governs your movement and balance.


The entorhinal region of the brain operates like a compass – certain cells keep track of the direction you are facing The entorhinal region of the brain operates like a compass – certain cells keep track of the direction you are facing


But how does our brain work out where we should go? How do we perform the equivalent of the mobile phone app that plots a route to your ultimate goal - your destination?

It’s a question that’s been the focus of recent research in Hugo Spiers’ lab. The results showed that calculations were going on in two areas of the brain. “It looks like the part of your brain that carries the grid cells also calculates the vector - the direction and distance - to the destination. Then the hippocampus, with the place cells, seems to be involved in calculating the route.”

Further research has shed light on our ability to sense where our destination is and home in on it. Spiers and collaborators investigated by scanning human brains using MRI (magnetic resonance imaging). “We were looking for patterns of activity indicative of the head direction cells. We thought that maybe we’d then find ‘goal direction cells’ that would provide a homing system,” he says. But there was a surprise in store.

Rather than two different parts of the brain, the activity was in the same area. In other words, the same set of cells were doing two jobs. “Rather than have one system that tells you which way you are facing and another that tells you which way you want to go, the system uses head direction cells to simulate the future,” explains Spiers.

To do it, the cells perform one task first and then the other. “The system spins your compass out of alignment just for a moment to think about the future, and then snaps back to the way you’re currently facing.”

The part of the brain where ‘goal direction’ takes place is the entorhinal/subicular region, which is damaged in patients suffering from Alzheimer’s. It’s possible in future that medical advances in treating the disease may come from studying the brain’s GPS. Indeed, a landmark study published earlier this year raises the prospect of treating another memory-related condition - post-traumatic stress disorder - by implanting memories.


Fig1_300dpi-1 A virtual simulation used by Hugo Spiers and colleagues in their work on ‘goal direction’ – how your brain knows where the destination is.


It sounds like the plot of the sci-fi film Total Recall but in March 2015, a team led by Karim Benchenane in Paris managed to do just that in the brains of sleeping mice. They did it by exploiting the ‘reward pathway’ - the brain mechanism stimulated when we derive pleasure from eating chocolate, for example. The scientists sent a burst of reward stimulation into the pathway whenever particular combinations of place cells were active.

The clever part about the experiment was that these chosen patterns of place cells corresponded to real-world locations. It resulted in a form of mind control. When they woke up, the mice much preferred the real-world locations associated with the reward. In all, they spent four to five times longer in those places than other mice, which had simply been given random stimulations.

“What’s so exciting is that this research shows us that place cells, which form the brain’s map, are used in deciding where to go. The fact that the scientists paired up cells with a reward, and the animal then chose to go there, implies that the decision-making draws on the knowledge of the map plus what’s associated with the map: the reward,” says Spiers.

Our understanding of just how we navigate from A to B has come a long way in the last four and a half decades. And with teams around the world studying the brain activity of both humans and animals, it’s likely that more fascinating revelations are just around the corner.

image credits: Chadwick et al., 2015 Current Biology

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