GPS in our brain
Nobel Prize in Physiology or Medicine 2014
Victoria Korzhova, "Biomolecule"
How do we determine our position in space? How do we find our way home from work every day, even when we go to the store on the way? The ability to navigate in space is one of the vital functions of the brain of all animals, but for a long time scientists could not agree on how the brain manages it. In 2014, the Nobel Prize in Physiology and Medicine was awarded to researchers of the "navigation system" of the brain.
Immanuel Kant in the Critique of Pure Reason suggested that some of the capabilities of the brain are provided by its innate qualities, including the ability to navigate in space and time. However, until almost the 1980s, neurophysiologists did not agree with the German thinker, suggesting that the navigation of animals in space is provided by a sequence of their perception of sensory stimuli and motor response. The works of John O'Keefe, May-Britt Moser and Edvard Moser helped to confirm Kant's assumption and describe the innate system of orientation in space. For their research, the scientists were awarded the Nobel Prize in Physiology or Medicine in 2014 "for the discovery of brain positioning system cells" – half of the prize was awarded to O'Keefe, and half to the Moser spouses.
The first scientist who supported the idea of the existence of a kind of "terrain map" in the brain was Edward Tolman, who studied the training of rats in navigation. In 1948, he suggested that after studying the surrounding space, a cognitive map is formed in the brain of an animal, which helps to choose the optimal route in the future [1]. At that time, few of his colleagues supported him; the behaviorists' idea had a strong position: the choice of the path is carried out due to successive motor reactions in response to external stimuli. Only ten years later, a method was developed that made it possible to test Tolman's hypothesis experimentally – implanting electrodes into the brain of animals for long-term recording of the activity of neurons.
Detecting "place cells"John O'Keefe began working at University College London in the late 1960s, after completing graduate studies at McGill University in Canada.
He used a new technique of implanted electrodes to record the activity of neurons in the hippocampus of rats, where he discovered the first element of the "GPS system of the brain" - "place cells" (also "spatial cells" in Russian) [2].
Although O'Keefe was not the first to record hippocampal neurons, he was the first to record normal animal activity, while other researchers used a limited set of behavioral tests. When O'Keefe allowed the animals to move freely around the cage, he noticed that some neurons behave very unexpectedly. Each of the group of these neurons was activated only when the animal was in a certain area of the cell, which was called the "field" of this neuron.
The scientist studied these amazing neurons – "place cells" – in more detail and found out that their reaction has nothing to do with sensory signals, and the combination of many "place cells" creates a complete map of the surrounding space (Fig. 1).
Figure 1. "Place cells". On the right is a schematic representation of the rat brain; orange marks the hippocampus, in which the "place cells" are located. On the left is a cage on which the rat can move freely; the lines show the animal's movement paths. When the rat is at the points marked in orange, a certain "place cell" is activated.O'Keefe's first publications and speeches with a story about amazing "place cells" and a mental map of space caused a skeptical reaction from his colleagues.
But the first experiments were followed by new confirmations, and by the early 1990s, the idea of the existence of a special navigation system in the brain had already entered textbooks. In the mid-2000s, the study of this system was developed in the works of the Moser spouses.
Opening of the "coordinate axis cells"After completing their postgraduate studies in their native Norway, May-Britt and Edward Moser spent about a year working abroad – first in Edinburgh, in the laboratory of Richard Morris, and then in London, in the laboratory of John O'Keefe.
In O'Keefe's lab, they became interested in studying the work of "place cells" and the role of the hippocampus in spatial orientation. After their return to Norway in 1996, they began new experiments to find out if any other brain areas were involved in the work of the mental map. At the same time, they improved O'Keefe's experimental setup, giving the rat the opportunity to move over sufficiently long distances (several meters, whereas O'Keefe's was 10-15 centimeters). Due to the presence of such a large field and the recording of neuronal activity in new areas in 2005, the Moser couple managed to discover a new component of the orientation system – "grid cells" in the entorhinal cortex (the area of the brain next to the hippocampus) (Fig. 2) [3].
Figure 2. "Cells of the coordinate grid". On the right is a schematic representation of the rat brain; blue indicates the entorhinal cortex, in which the "cells of the coordinate grid" are located. On the left is a cage where the rat can move freely. The lines show the animal's movement paths; when the rat is at the points marked in blue, a certain "grid cell" is activated. Together, these points form a hexagonal grid.The behavior of the "grid cells" turned out to be even more surprising than the behavior of the "place cells".
The individual neurons described by the Mosers were activated when the rat was at several points in the field. At the same time, together these points of the field formed a hexagon, and together with the points of activity of other neurons – a whole hexagonal network, which is why these neurons got their name. Such a network, covering the entire surrounding space, helps the brain to determine distances, and not just the position of the animal in space.
Other elements of the "GPS brain system"The research of O'Keefe and Moser aroused great interest among neurophysiologists and prompted many scientists to turn to this topic.
Gradually, other elements of this internal orientation system were discovered – "head direction cells" located at the base of the hippocampus (subiculum), and "edge cells" (border cells) located in the hippocampus and nearby areas of the brain (hippocampal formation). The "direction cells" work like a compass, determining which way the animal's head is pointing. "Edge cells" help to "mark on the map" the location of the walls that limit the territory. In addition, cells with mixed activity were found (Fig. 3).
Figure 3. Different cells of the navigation system:
"place cells" in the hippocampus (A),
"direction cells" in the subiculum (B),
"cells of the coordinate grid" in the entorhinal cortex (B).
In recent years, researchers have learned a lot about how the orientation system of the brain works, and now they can explain in much more detail how animals create a mental map of the surrounding area. Another confirmation that Kant was right in his reasoning about human perception of space is the recent discovery of the innateness of the spatial system of the brain. In 2010, two teams of researchers independently discovered that small rats who went for a walk for the first time in their lives already have normally functioning "place cells" and "direction cells", and only "grid cells" appear a little later. It turns out that the main components of the spatial perception system are formed in mammals even before they acquire any navigation experience [4].
The orientation system was first discovered in rats; it was later described in mice and other mammals, including bats and monkeys. Moreover, it turned out that the work of these cells may vary slightly depending on the characteristics of animal behavior. In bats that actively move in three-dimensional space (whereas mice and rats in two-dimensional), the "fields" of place cells are not flat zones, but three-dimensional regions of space [5].
Figure 4. Different types of neurons located in the hippocampus and entorhinal cortex form a common navigation system in the brain. Studies show that the navigation system in the brain of a rat and a human is arranged according to a general principle.In experiments conducted in the treatment of patients with epilepsy, neurons similar to "place cells" and "grid cells" were found in the corresponding areas of the brain.
This is confirmed by experiments using fMRI. The data available at the moment suggest that the orientation system is a conservative system of the brain of all vertebrates.
A new stage in the study of the brain and neurocomputersThe discoveries of O'Keefe and the Mosers are undoubtedly one of the most significant in neuroscience in recent decades.
Thanks to their research, scientists got acquainted with a completely new type of neuronal work, in which cells form a multicomponent network that allows complex cognitive processes to be carried out.
In addition to the fundamental importance, the study of the orientation system of the brain plays an important role for clinical practice. Some diseases of the nervous system, for example, Alzheimer's disease, are accompanied by a violation of spatial orientation and spatial memory.
The study of the work of complex neural structures is important for the rapidly developing field of neurocomputers and robotics, allowing the use of elegant natural solutions as technological finds.
Written using materials from the Nobel Committee.
LiteratureTolman E.C. (1948).
- Cognitive maps in rats and men. Psychol. Rev. 55, 189-208;
- O’Keefe J., Dostrovsky J. (1971). The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 34, 171-175;
Hafting T., Fyhn M., Molden S., Moser M.B., Moser E.I. (2005). Microstructure of a spatial map in the entorhinal cortex. Nature 436, 801-806; - Elements: "The idea of space is innate";
- Yartsev M.M., Ulanovsky N. (2013). Representation of three-dimensional space in the hippocampus of flying bats. Science 340, 367-372.
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