The significant discovery of ‘brain’s internal GPS’

The discovery of the brain’s positioning system represents a paradigm shift in our understanding of how ensembles of specialised cells work together to execute high cognitive functions

Steve Connor

(From left) John O’Keefe found the “place cells” of the brain, while May-Britt & Edvard Moser built on his research

THREE foreign-born scientists who have all worked in the UK have jointly won this year’s Nobel Prize in Physiology or Medicine for their pioneering research into how the “GPS” of the brain creates internal maps of the real world. John O’Keefe, who was born in New York to Irish immigrants, but who has worked at University College London for more than 40 years, shares the prize with husband-and-wife team May-Britt and Edvard Moser, Norwegian nationals who were trained at Professor O’Keefe’s laboratory in London.

The three researchers share this year’s prize, “for their discoveries of cells that constitute a positioning system in the brain” according to the citation from the Nobel Assembly at the Karolinska Institute in Stockholm, which pointed out that philosophers have argued for centuries about how we know where we are.

“This year’s Nobel Laureates have discovered a positioning system, an ‘inner GPS’ in the brain that makes it possible to orient ourselves in space, demonstrating a cellular basis for higher cognitive function,” the Karolinska said. “The discovery of the brain’s positioning system represents a paradigm shift in our understanding of how ensembles of specialised cells work together to execute high cognitive functions. It has opened up new avenues for understanding other cognitive processes, such as memory, thinking and planning,” it said. An attack on the brain’s positioning system occurs in some neurological illnesses, such as Alzheimer’s disease where the progressive degeneration of the neurons of the brain results in patients becoming disoriented after losing their memory of spatial locations.

Professor O’Keefe, director of the Sainsbury Wellcome Centre for Neural Circuits and Behaviour at UCL, discovered the first components of the brain’s internal positioning system when he found a type of cell in the brain’s hippocampus that was always activated when a laboratory rat was at a certain place in a room.

“This part of the brain is one of the first areas to be attacked in Alzheimer’s disease,” Professor O’Keefe said.

In a study published in 1971, Professor O’Keefe suggested that these “place cells” were used by the brain to build up a map of the environment. More than three decades later, in 2005, May-Britt and Edvard Moser discovered other nerve cells in a nearby part of the brain, called the entorhinal cortex, that were activated when the rat passed certain locations.

The two researchers, working at the Norwegian University of Science and Technology in Trondheim, found that these locations formed a hexagonal grid, with each “grid cell” within the entorhinal cortex reacting in a unique spatial pattern – collectively the grid cells form a coordinated system that allowed spatial navigation through a complex maze.

The two findings, together with other discoveries, allowed the scientists to discover how mammals, including humans, were able to build up an internal map of the environment to locate their position and work out how to get from one place to another.

John Stein, emeritus professor of physiology at Oxford University, said: “I remember how great was the scoffing in the early 1970s when John first described place cells. ‘Bound to be an artifact’, ‘he clearly underestimates rats' sense of smell’ were typical reactions. Now, like so many ideas that were at first highly controversial, people say ‘well that's obvious’.” Professor Andrew King of Oxford University said: “The discovery by John O’Keefe that neurons in the hippocampus revolutionised our understanding of how the brain knows where we are and is able to navigate within our surroundings."

Professor O’Keefe said he was “totally delighted and thrilled” to have received the award, which he heard about this morning before he left for his laboratory in central London. “It’s the highest accolade and a terrific sign of the way the world thinks about our work. UCL is a terrific place to do research,” he said. Professor O’Keefe receives half the prize money of 8m Swedish Kroner, and the Mosers share the other half, in recognition of his seminal role in the joint effort. — The Independent