The neuroscientists John O´Keefe from University College London and May-Britt Moser and Edvard Moser from the Norwegian University of Science and Technology in Trondheim are this year’s Nobel laureates in Physiology or Medicine. Together (although more than 30 years apart) they helped us understand how we know where we are, how we know the way from one place to another, and how we store this information in order to immediately find the way when we repeat a path. They call it our “inner GPS” – the brain’s positioning system – and it is a groundbreaking discovery.

The first step towards the discovery of this system was taken in 1971, when John O´Keefe described its first component. He found that certain neurons in the hippocampus fired whenever a rat was in a certain place in the local environment, with neighboring neurons firing at different locations, such that the entire environment was represented by the activity of these cells throughout the hippocampus.  

O´Keefe called these neurons “place cells” and showed that they were able to form an inner map of the environment, drawn by the pattern of place cell activation in the hippocampus. He later showed that the firing rate of these place cells could be affected not only by the rat’s position in the maze, but also by visual input or by olfactory input, either because it found something new or found something missing from that specific location.

O´Keefe also found that there were other cells that would signal changes in the rat’s position relative to the environment. His studies showed that the combined activity of specific place cells build the memory of that environment in the form of a cognitive map.

An upgrade to the discovery of place cells came in 2005, when May-Britt and Edvard Moser presented another key component of this neuronal positioning system, the “grid cells”.

They discovered a pattern of activity in an area of the brain close to the hippocampus called the entorhinal cortex. Here, certain cells were activated at specific locations, similarly to place cells, but that each of these cells was activated by multiple locations. These locations formed a grid that covered the entire environment explored by the animal, indicating that they could generate a coordinate system that allowed 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 that give rise to the brain’s positioning system.

Although these studies were all conducted in rats, evidence from brain imaging techniques and from patients who have undergone neurosurgery has indicated that place and grid cells also exist in humans. Also, in patients with Alzheimer´s disease, both the hippocampus and the entorhinal cortex are frequently affected at an early stage of disease development, when these patients start losing their way and their ability to recognize the environment.

So, besides the very important knowledge about the brain´s positioning system per se, these findings may also help us understand how patients with Alzheimer´s disease develop spatial memory loss and, eventually, how to overcome it.

As the Nobel Committee for Physiology or Medicine stated, this discovery “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.”

References

Colgin LL, Moser EI, & Moser MB (2008). Understanding memory through hippocampal remapping. Trends in neurosciences, 31 (9), 469-77 PMID: 18687478

Hafting T, Fyhn M, Molden S, Moser MB, & Moser EI (2005). Microstructure of a spatial map in the entorhinal cortex. Nature, 436 (7052), 801-6 PMID: 15965463

Moser EI, Kropff E, & Moser MB (2008). Place cells, grid cells, and the brain’s spatial representation system. Annual review of neuroscience, 31, 69-89 PMID: 18284371

Moser EI, & Moser MB (2008). A metric for space. Hippocampus, 18 (12), 1142-56 PMID: 19021254

Moser EI, Roudi Y, Witter MP, Kentros C, Bonhoeffer T, & Moser MB (2014). Grid cells and cortical representation. Nature reviews. Neuroscience, 15 (7), 466-81 PMID: 24917300

O’Keefe J, & Dostrovsky J (1971). The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain research, 34 (1), 171-5 PMID: 5124915

O’Keefe J (1976). Place units in the hippocampus of the freely moving rat. Experimental neurology, 51 (1), 78-109 PMID: 1261644

Sargolini F, Fyhn M, Hafting T, McNaughton BL, Witter MP, Moser MB, & Moser EI (2006). Conjunctive representation of position, direction, and velocity in entorhinal cortex. Science (New York, N.Y.), 312 (5774), 758-62 PMID: 16675704

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