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Nobel prize for decoding brain’s sense of place

Discoverers of brain’s navigation system get physiology Nobel.

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Christian Charisius/dpa/Corbis; David Bishop/UCL

From left: Edvard Moser, May-Britt Moser and John O’Keefe.

Brain cells that make up the biological equivalent of a satellite-navigation system have garnered three scientists the 2014 Nobel Prize in Physiology or Medicine. The discovery of the cells sheds light on one of neuroscience’s great mysteries — how we know where we are in space.

John O’Keefe of University College London won half of the prize for his discovery in 1971 of ‘place’ cells in the hippocampus, a part of the brain associated with memory. Edvard and May-Britt Moser, who are married and jointly run a lab at the Kavli Institute for Systems Neuroscience in Trondheim, Norway, share the other half for their 2005 discovery of ‘grid’ cells in an adjacent brain structure, the entorhinal cortex. Along with other navigation cells, grid and place cells allow animals to keep track of their position. Both cell types were discovered in rats, but have since been found in humans.

“Understanding where we are in space is one of the most fundamental issues for survival,” says Tobias Bonhoeffer, director of the Max Planck Institute of Neurobiology in Martinsried, Germany.

The discoveries will also be key to answering the broader question of how the brain makes sense of the world, says neuro­scientist Botond Roska of the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland. “These are three deep-thinking people who have changed the way we think about the brain,” he says.

Most neuroscientists once doubted that brain activity could be linked with behaviour, but in the late 1960s, O’Keefe began to record signals from individual neurons in the brains of rats moving freely in a box. He put electrodes in the hippocampus and was surprised to find that individual cells fired when the rats moved to particular spots. He concluded that the memory of an environment may be stored as a specific combination of place-cell activities in the hippo­campus (J. O’Keefe and J. Dostrovsky Brain Res. 34, 171–175; 1971). “I realized that if you put them all together, you could have something like a map,” says O’Keefe.

Fast-forward to the 1990s, and his work attracted the attention of the Mosers, then PhD students at the University of Oslo. They joined him in London as postdocs, but within months they had moved to the Norwegian University of Science and Technology in Trondheim to set up their own lab. There they discovered that some cells in the entorhinal cortex fire when rats pass the points of a hexagonal grid. They found out that the brain uses this pattern as a coordinate system for spatial navigation (T. Hafting et al. Nature 436, 801–806; 2005).

The pattern constitutes what is known as a neural code. It is the only one known to be generated entirely in the brain, marking a milestone for computational neuroscience (see page 154).

Both place and grid cells have practical relevance. The early stages of Alzheimer’s disease affect the entorhinal cortex, and one of the first symptoms is losing one’s way. The disease goes on to devastate the hippocampus, stripping sufferers of their memories. “It is a good example of how very basic research can help us gain the deeper understanding we need in such devastating diseases to move towards therapies,” says Richard Morris, a memory researcher at the University of Edinburgh, UK.

May-Britt was presiding over a lab meeting when the call came from the Nobel committee in Stockholm. “I hesitated to answer it,” she told Nature, laughing. “But I did — and I couldn’t believe it; I even cried.” Edvard’s excitement was delayed: he was on a aeroplane to Munich, Germany, when his wife got the call. O’Keefe heard the news while working on a grant revision at home. “I’m totally delighted and thrilled,” he said in front of a phalanx of television cameras at a London press conference.

The Mosers once described their time in O’Keefe’s lab as “probably the most intense learning experience in our lives”. O’Keefe has similar memories. “It was intense — because they’re intense. They’re absolutely superb scientists.”

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  • This story appeared in print under the headline ‘Prize for place cells’

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