Ever wondered what’s happening in our brains when we get lost or explore a new place? The Nobel Prize in Physiology for the year 2014 was awarded for some of the answers to this problem which had been puzzling scientists for almost a century.
Like the GPS in our phones and cars, our brain has a sophisticated positioning system. The brain integrates sensory data and knowledge of our current position to judge where we are headed. Only when we are lost or suffer from neurodegenerative diseases do we realise how critical our positioning system is to our survival.
The tracking and positioning systems of the mammalian brain was being studied for a long time. For example, the simple roundworm (Caenorhabditis elegans), with just 302 neurons, finds its way around solely by olfactory signals. It follows the path of an increasing or decreasing odour gradient. Honeybees, on the other hand, calculate its position by integrating its direction and speed of movement, without keeping track of landmarks or external cues. Vertebrates have even more sophisticated positioning systems.
Recent research in the area reveal neural maps in the brains of mammals, which are collections of neurons which fire in specific patterns corresponding to the surroundings and the animal’s position in it.
The 2014 Nobel Prize in Physiology or Medicine was awarded to Dr. John M. O’Keefe, Dr. May-Britt Moser and Dr. Edvard I. Moser for their discoveries of nerve cells in the brain that enable a sense of place and navigation. Until the 1930s, research done on lab mice in mazes led to the belief that they memorised a long sequence of lefts and rights to find their way around. Edward C Tolman, physiology professor at the University of California from 1918 to 1954, observed the animals take shortcuts or make detours that would not be expected had they just memorised one long sequence of behaviour. This led to the hypothesis that the rats formed a sort of mental map of its surroundings, corresponding to the spatial geometry around it. Tolman’s ideas remained controversial for decades. His ideas did not gain much ground up until the 1950s, when it became possible to insert electrodes into the brains of awake mammals to record firing patterns of individual neurons.
A cell fires when it triggers an action potential- a short change in the potential difference across the cell membrane. Dr. John M. O’Keefe studied the brain’s hippocampus, a region in the brain associated with memory and spatial navigation (On a side note, the Hippocampus is one of the first regions to be affected by the Alzheimer’s disease). He inserted electrodes into a rat’s Hippocampus, and noticed that certain cells fired when the rat was at a particular location. He called them ‘Place cells’. It was seen that the firing pattern of a handful of such place cells precisely identified the animal’s location. In 1978, O’Keefe and his colleague suggested that place cells were an integral part of the mental map Tolman envisaged.
Neuroscientists of that era speculated that the hippocampus was too far removed from the sensory cortex (The part of the brain which handles the sensory inputs) to process their information in any meaningful way that could be understood by simple electrodes. O’Keefe’s observations dashed that speculation. It was then hypothesised that the area where place cells were located, namely the CA1 region, in the hippocampus received its location cues from other parts of the hippocampus rather than directly from the sensory cortex. To verify the hypothesis, O’Keefe and his colleagues disrupted the communication channels between the CA1 region and the region of the hippocampus known to feed information to the CA1. Surprisingly, the neurons in the CA1 fired as before, when the rat reached specific locations. The inescapable conclusion was that the CA1 received its location cues from the entorhinal cortex, an adjoining area of the brain with a direct interface with the hippocampus.
Electrodes were inserted into the entorhinal cortex, and the firing patterns studied. The cells over there fired much like the place cells, but a single cell also happened to fire at multiple locations! This observation was made in 2002. By 2005, O’Keefe and his team observed something spectacular about the firing patterns- the locations at which one particular cell fired were the vertices of a regular hexagon! These cells were dubbed grid cells. It was soon apparent that the entire enclosure where the rat was kept was divided into hexagonal grids. As these grid cells were further studied, more patterns were observed- the grid cells in the dorsal side fires at compact hexagons, while those lower down in the ventral side fired at hexagons of larger edge. The different layers of grid cells in the entorhinal cortex fired at hexagons of different size, each layer forming one with approximately 1.4 times the edge length of the hexagon in the layer above. This is strongly reminiscent of the smaller squares and the bigger ones in the Cartesian coordinates. For example, the top layer fired at hexagons 30 to 35 cm in length, the next layer at 42 to 49 cm, and so on. The lower layers represented hexagons several meters across.
Direction cells and Border cells were also discovered in the entorhinal cortex – the direction cells fire when the rodent faces a particular direction, and the border cells fire when the rat is facing a wall. The firing patterns seemed to reflect the distance from the wall or the edge of an enclosure. In 2008, another long sought out cell was discovered- the speed cells. The firing rates of these cells increased in proportion to its running speed. These cells were believed to provide the grid cells updated information on the rodent’s position. It was observed that the place cells in the hippocampus rapidly assumes a new location to fire as soon as the rat was put in a new enclosure. However, the grid cells was found to fire at analogous positions in the new enclosure. The grid cells, in some sense, formed a coordinate system that did not change from one enclosure to the other. The firing patterns from the entorhinal cortex was imported to the hippocampus and used to link the place cells to a particular location. It is now believed that the hippocampus stores not just the position, but also the events that occur at that particular place. Particulars about an event are fused with the coordinates and are laid down in the animal’s memory.
However, the scientific world is still pretty much in the dark as to how this information is used by the rest of the brain’s systems or the evolutionary origins of this intricate mechanism. The location systems of the brain and the mechanisms of memory formation will undoubtedly be a fascinating area of research for many years to come.comments powered by Disqus