The 2014 Nobel Prize in Physiology and Medicine

© Shutterstock
© Shutterstock
At all times, the following questions have stirred up scientists’ and philosophers’ curiosity : « How can I know where I am? How can I map the environment surrounding me? How can I orient myself through a complex environment? How can I go from one place to another and remember it the next time I trace the same path?”.
Three searchers, on a half John O’Keefe and on the other half jointly May-Britt Moser and Edvard I. Moser, have answered some of these questions via their discoveries of nerve cells in the brain that enable a sense of place and navigation, constituting a positioning system – an “inner GPS” – in the brain. This exposure allowed them to receive the 2014 Nobel Prize in Physiology and Medicine on October 6th.

Place and navigation through the time

During the XVIIIth century, the German philosopher Immanuel Kant argued that, independently of experience, some mental abilities exist as a priori knowledge. He was the first one to think about the concept of space. Indeed, he considered it as an inbuilt principle of the mind through which the environment is and must be perceived.

In the 40’s, with the advent of behavioural psychology, Edward Tolman examined rats moving through labyrinths and found that they could learn how to navigate. He therefore proposed that a « cognitive map » formed in the brain could help them to find their way through a complex environment. However, his work did not explain how this map was represented into the brain.

During the last quarter of the XXth century, John O’Keefe together with May-Britt and Edvard I. Moser were able to find this representation, demonstrating a cellular basis for higher cognitive function. As mentioned in the scientific background – “The brain’s navigational place and grid cell system” – published by the Nobel Prize comity “The work by John O’Keefe, May-Britt Moser and Edvard Moser has dramatically changed our understanding of how fundamental cognitive functions are performed by neural circuits in the brain and shed new light onto how spatial memory might be created.”

John O’Keefe and the “place cells”: the cognitive map theory

In 1971, the scientist John O’Keefe decided to study the positioning system – using neurophysiological methods – by analyzing rats moving freely into a room.

He found that some nerve cells – located in the hippocampus – were always activated at a certain place in the room, whereas other were activited at other places. He therefore discovered the first component of the system : the “place cells” able to form an inner map of the environnement. He also showed that these cells might be involved in measuring distance under some circumstances.

Moreover, he discovered that the rat’s brain was able to stock multiple maps. Indeed, a specific serial combination of activity in different place cells represents a unique environment while an other combination represents an other environment. He supposed that once the mapping of the place cells was established, it could be stable over time, suggesting that place cells might be involved in memory functions.

May-Britt Moser, Edvard I. Moser and the “grid cells”: a spatial metric coordination system

Several decades after John O’Keefe’s discovery, May-Britt and Edvard Moser identified, in 2005, the second component involved in the positioning system by mapping the connections to the hippocampus in rats moving in a room.

Indeed, the both scientists discovered another type of nerve cell. These cells generate an internal coordinate system, allowing a precise positioning and pathfinding. They are called the “grid cells” and are found in the medial entorhinal cortex. As for the place cells, each of these grid cells are activated in a unique spatial pattern meaning that only certain grid cells are activated when the rat passes certain locations. Collectively, these locations form nodes of an extended hexagonal grid constituting a coordinate system that allows for spatial navigation.

Moreover, together with other cells of the entorhinal cortex which recognize the direction of the animal’s head  – head direction cells – and the room borders – border cells -, they form interconnected networks with hippocampal place cells. This circuitry makes it possible to determine position and to navigate.

Finally, thanks to brain imaging techniques and patients undergoing neurosurgery, the existence of these cells types has been proved in other mammals including humans.

New avenues for reserach in cognitive neuroscience

As explained by the Nobel Prize comity “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.”

Moreover, brain disorders currently represent the most common cause of disability. However, even if degenerative diseases are very handicapping, there is still no effective way to prevent or cure most of them. In various disorders, such as Alzheimer’s disease, the episodic memory is affected since the hippocampus and the entorhinal cortex are one of the first structures to be affected leading to a non environment recognition. At the moment more than 25 millions of patients have caught it and this number must double in the next twenty years according to the World Health Organization (WHO).

Therefore a better understanding of brain’s navigational system might help to understand the cognitive decline seen in patients with this disease. The discoveries exposed in this Nobel Prize have been a  major leap forward to prevent or even better find a cure for these disease.

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