The Nobel Prize in Physiology or Medicine 2014 has been divided among three scientists with one half being awarded to John O'Keefe of University College, London, and the other half shared by May-Britt Moser of the Centre for Neural Computation, Trondheim, Norway and Edvard I. Moser of Kavli Institute for Systems Neuroscience, Trondheim, Norway “for their discoveries of cells that constitute a positioning system in the brain.”
Their discoveries tell us how we are able to get a sense of place in any given environment and an ability to navigate. If the sense of place gives us a perception of the position with respect to the environment, the ability to navigate is linked to the direction and distance from the previous positions. In effect, the two together provide us with an internal positioning or “inner GPS” with respect to the environment.
American experimental psychologist Edward Tolman was the first to propose, as early as 1948, a concept of a map-like representation of a place in the brain. However, he did not propose where these functions were located in the brain and how they functioned.Place cells
The first success in understanding the sense of place came from O’Keefe’s experiments using freely moving animals. The cellular activity in the brain of these animals as they moved allowed him to find the unique place fields and relate the neural activity to the sense of place. The neural activity was seen in the hippocampus of the brain.
O’Keefe also showed that a specific rearrangement of place cells in different settings, called remapping, could be learned, the reason why we are able to place ourselves in an environment and navigate after some time. In effect, the place cells acted as a substrate for memory process, where memory of an environment was based on specific combination of place cells.Seminal work
Although O’Keefe was not the first to propose that the hippocampus was responsible for spatial navigation, it was received with scepticism. It soon came to be accepted that the hippocampus contains the mental map or inner map. The discovery of place cells and the demonstration that they represented a mental map, together with the proposal that the hippocampus containing the neural cells provides the inner map that store information of the environment were seminal.
O’Keefe’s work led to a flood of studies, both experimental and theoretical, including those of the Moser couple.
Despite the notion that the place cells originated within the hippocampus, May-Britt Moser and Edvard I. Moser went beyond O’Keefe’s work. They looked for areas in the brain outside the hippocampus where place cell firing was generated. After all, the entorhinal cortex, which lies on the dorsal side of the hippocampus, provided a major input to the hippocampus.
According to the Nobel Prize site, “A large part of the output from the entorhinal cortex projects to the dentate gurus in hippocampus, which in turn connect to the region in the hippocampus called CA3, and further to CA1 in the dorsal hippocampus.” The place cells are found in the CA1.
The two scientists were prompted to look for place coding cells in the entorhinal cortex as it was directly and reciprocally connected to CA1 through CA3. Like others before them, May Britt Moser and Edvard Moser established that entorhinal cortex contained cells that “shared characteristics” with the place cells in the hippocampus.Grid cells
Looking for place cells in the entorhinal cortex, these two researchers discovered a novel cell type — grid cells. The gird cells together with the place map provide the inner map. If the place cells provide the spatial map, the grid cells provide the navigation or path integration system.
A single grid cell fires when an animal reaches particular locations in an arena. These locations are arranged in a hexagonal pattern. They also showed that the grid formation did not arise out of a simple transformation of sensory or motor signals, but out of complex network activity.
“They concluded that the grid cells were part of a navigation or path integration system. The grid system provided a solution to measuring movement distances and added a metric to the spatial maps in the hippocampus,” notes the advanced information provided by the Nobel Prize site.
They also found that the grid cells were “embedded in a network in the medial entorhinal cortex of head direction cells and border cells, and in many cases, cells with a combined function.” The head-direction cells are like a compass that becomes active when the animal’s head turns in certain direction. The border cells, on the other hand, provide a reference to the wall or boundary of a room or environment.
All the three cells — the grid cells, the head-direction cells and border cells — projected to the hippocampus place cells.
The Mosers’ discovery of the gird cells, its spatial metric co-ordination system and the identification of the medial entorhinal cortex as a computational centre for spatial representation has been a breakthrough.
Though the presence of place cells and grid cells were identified experimentally in rats, such a system is found in other animals too, including humans. The hippocampal-entorhinal structure is found in all mammals and a hippocampal-like structure is found in non-mammals with navigational capacity. This suggests that the functional and robust grid-place cells system in vertebrates must have been conserved.
The existence of place-like cells in the hippocampus and grid-like cells in the entorhinal cortex has been identified in the human brains of patients with epilepsy. Results from functional imaging (fMRI) studies on human brains have provided support for the existence of place cells and grid cells in humans. Also, studies of patients undergoing neurosurgery have strengthened the evidence of place cells and grid cells in humans.
The discovery of place cells and grid cells and their role in spatial mapping and navigation have great implications in medicine. The reason why patients with Alzheimer’s disease often lose their way and cannot recognise the environment becomes clear as the hippocampus and entorhinal cortex, where the place cells and grid cells are located, are frequently affected at an early stage.
(Rewritten based on advanced information available in Nobel Prize website)