Norwegian Nobel Prize Winners in Medicine 2014 Discover Our Inner Positioning System

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The Nobel Prize in Physiology or Medicine 2014 was divided, one half awarded to John O’Keefe from New York, the other half jointly to the Norwegian researchers May-Britt and Edvard Moser “for their discoveries of cells that constitute a positioning system in the brain”.

How do we know where we are? How can we find the way from one place to another? And how can we store this information in such a way that we can immediately find the way the next time we trace the same path? 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.

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In 1971, John O’Keefe discovered the first component of this positioning system. He found that a type of nerve cell in an area of the brain called the hippocampus that was always activated when a rat was at a certain place in a room. Other nerve cells were activated when the rat was at other places. O’Keefe concluded that these “place cells” formed a map of the room.

More than three decades later, in 2005, May-Britt and Edvard Moser discovered another key component of the brain’s positioning system. They identified another type of nerve cell, which they called “grid cells”, that generate a coordinate system and allow for precise positioning and pathfinding. Their subsequent research showed how place and grid cells make it possible to determine position and to navigate.

The discoveries of John O’Keefe, May-Britt Moser and Edvard Moser have solved a problem that has occupied philosophers and scientists for centuries – how does the brain create a map of the space surrounding us and how can we navigate our way through a complex environment?

How do we experience our environment?
The sense of place and the ability to navigate are fundamental to our existence. The sense of place gives a perception of position in the environment. During navigation, it is interlinked with a sense of distance that is based on motion and knowledge of previous positions.

Questions about place and navigation have engaged philosophers and scientists for a long time. More than 200 years ago, the German philosopher Immanuel Kant argued that some mental abilities exist as a priori knowledge, independent of experience. He considered the concept of space as an inbuilt principle of the mind, one through which the world is and must be perceived. With the advent of behavioural psychology in the mid-20th century, these questions could be addressed experimentally. When Edward Tolman examined rats moving through labyrinths, he found that they could learn how to navigate, and proposed that a “cognitive map” formed in the brain allowed them to find their way. But questions still lingered – how would such a map be represented in the brain?

John O’Keefe and the place in space
John O’Keefe was fascinated by the problem of how the brain controls behaviour and decided, in the late 1960s, to attack this question with neurophysiological methods. When recording signals from individual nerve cells in a part of the brain called the hippocampus, in rats moving freely in a room, O’Keefe discovered that certain nerve cells were activated when the animal assumed a particular place in the environment (Figure 1). He could demonstrate that these “place cells” were not merely registering visual input, but were building up an inner map of the environment. O’Keefe concluded that the hippocampus generates numerous maps, represented by the collective activity of place cells that are activated in different environments. Therefore, the memory of an environment can be stored as a specific combination of place cell activities in the hippocampus.

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May-Britt and Edvard Moser find the coordinates

The Norwegian Nobel Prize Winners in Medicine 2014, May-Britt and Edvard Moser, were mapping the connections to the hippocampus in rats moving in a room when they discovered an astonishing pattern of activity in a nearby part of the brain called the entorhinal cortex. Here, certain cells were activated when the rat passed multiple locations arranged in a hexagonal grid (Figure 2). Each of these cells was activated in a unique spatial pattern and collectively these “grid cells” constitute a coordinate system that allows for spatial navigation. Together with other cells of the entorhinal cortex that recognize the direction of the head and the border of the room, they form circuits with the place cells in the hippocampus. This circuitry constitutes a comprehensive positioning system, an inner GPS, in the brain (Figure 3).

A place for maps in the human brain
Recent investigations with brain imaging techniques, as well as studies of patients undergoing neurosurgery, have provided evidence that place and grid cells exist also in humans. In patients with Alzheimer’s disease, the hippocampus and entorhinal cortex are frequently affected at an early stage, and these individuals often lose their way and cannot recognize the environment. Knowledge about the brain’s positioning system may, therefore, help us understand the mechanism underpinning the devastating spatial memory loss that affects people with this disease.

The discovery of the brain’s positioning system represents a paradigm shift in our understanding of how ensembles of specialized cells work together to execute higher cognitive functions. It has opened new avenues for understanding other cognitive processes, such as memory, thinking and planning.

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Alfred Nobel had an active interest in medical research. Through Karolinska Institutet, he came into contact with Swedish physiologist Jöns Johansson around 1890. Johansson worked in Nobel’s laboratory in Sevran, France during a brief period the same year. Physiology or medicine was the third prize area Nobel mentioned in his will.

The Nobel Prize in Physiology or Medicine is awarded by the Nobel Assembly at Karolinska Institutet, Stockholm, Sweden.

567 Nobel Prizes!

Between 1901 and 2014, the Nobel Prizes and the Prize in Economic Sciences were awarded 567 times.

Nobel Prize Number of Prizes Number of Laureates Awarded to one Laureate Shared by two Laureates Shared by three Laureates
Physics 108 199 47 31 30
Chemistry 106 169 63 22 21
Medicine 105 207 38 31 36
Literature 107 111 103 4
Peace 95 103+25 64 29 2
Economic Sciences 46 75 23 17 6
Total: 567 889 338 134 95