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Biological Chemistry

Nobel Prize In Physiology Or Medicine

Awards: John O’Keefe, May-Britt Moser, and Edvard Moser win for discovering the brain’s mapping system

by Carmen Drahl
October 9, 2014 | A version of this story appeared in Volume 92, Issue 41

GETTING SOME BEARINGS
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Credit: Nobelprize.org
As a rat (black oval) navigates around a lab arena, place cells fire when the animal reaches a particular location (orange field). Meanwhile, a single grid cell in the entorhinal cortex fires when the rat reaches locations in a distinct hexagonal pattern (blue fields).
Place cell (orange) and grid cell (blue) systems work simultaneously to give a rat a comprehensive positioning system in their brain.
Credit: Nobelprize.org
As a rat (black oval) navigates around a lab arena, place cells fire when the animal reaches a particular location (orange field). Meanwhile, a single grid cell in the entorhinal cortex fires when the rat reaches locations in a distinct hexagonal pattern (blue fields).

This year’s Nobel Prize in Physiology or Medicine was awarded to John O’Keefe, May-Britt Moser, and Edvard Moser, for discovering the networks of cells that form the brain’s navigational system. This fundamental work in neuroscience could have applications in Alzheimer’s and other diseases.

For hundreds of years, questions about how humans understand their location in their environment, and how they develop a sense of distance, have intrigued scientists and philosophers alike. It was 20th-century advances in psychology and neuroscience that allowed researchers to probe their questions experimentally.

Once scientists understood that rats could learn to find their way through a maze, they sought the areas of the brain responsible for this behavior. In 1971, by recording electrical signals from individual nerve cells, John O’Keefe of University College London found cells in the hippocampus region of the brain that were active only when rats were in a certain place in their environment. He concluded the activity of these cells must form an inner map of the rat’s whereabouts and dubbed them “place cells.”

O’Keefe
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Credit: David Bishop/UCL
John O’Keefe of UCL – recipient of the 2014 Nobel prize in medicine/physiology.
Credit: David Bishop/UCL
May-Britt and Edvard Moser
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Credit: Körber Foundation/Friedrun Reinhold
May-Britt and Edvard Moser, recipients of the 2014 Nobel prize in medicine/physiology.
Credit: Körber Foundation/Friedrun Reinhold

O’Keefe’s work “opened up a whole area of research about how the hippocampus contributes to memories,” says Oxford University physiologist and neuroscientist John Stein. “To navigate, you have to remember where you are.”

In 2005, May-Britt and Edvard Moser, a husband-wife team at the Norwegian University of Science & Technology, in Trondheim, built on O’Keefe’s and others’ work. They discovered that nerve cells in the entorhinal cortex, a region near the hippocampus, fired when a rat scuttled past particular locations arranged in a hexagonal grid. These “grid cells” work with place cells as well as other cells to form the brain’s positioning system.

The Mosers briefly worked in O’Keefe’s lab in 1995. “They were already clearly destined to be stars,” O’Keefe told Nobelprize.org.

The human brain’s spatial navigation system appears to be composed of similar nerve cells. And because the entorhinal cortex, the location of grid cells, is often damaged during the first phases of Alzheimer’s disease, the work may explain why the disease’s early symptoms include getting lost.

May-Britt Moser almost didn’t take the Nobel Committee’s call because she was in a meeting. Meanwhile, Edvard Moser was on a flight when the prize was announced. “I had no idea what was going on when I was welcomed at the airport with flowers,” he told a Swedish news agency.

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