Generations of scientists have pored over a seemingly basic but ultimately complex skill: how are humans able to find their way from one spot to another?
Little by little, the fog of mystery is beginning to dissipate, thanks to work revealing the key areas in the brain that enable us to orientate ourselves and navigate.
On Monday, the 2014 Nobel Prize for Medicine went to a trio of scientists who identified the brain cells essential to this task.
In the early 1970s, John O'Keefe, a British-American neuroscientist, discovered "place" cells that are triggered when the brain perceives it is in a specific location.More than three decades later, a Norwegian couple, May-Britt and Edvard Moser, found "grid" cells, which, like step-points on a map, enable the mind to work out a path to a destination.
Together, the two types of cells form inter-connected networks without which we would not know where we were or be able to find our way.
The research may one day help treat neurodegenerative conditions that leave people unable to manage even the most basic tasks.
- 'Great scoffing' -
The breakthrough came in 1971, when O'Keefe observed that specific neurons in the hippocampus area, which is linked to memory, fired whenever a lab rat, with electrodes inserted in the brain, reached a particular spot in a room.
When the rodent moved to another area, different cells lit up -- each cell was thus associated with a specific location.This pattern of cell activity, observed with the help of electrodes in the brain, created a sort of brain map of the environment, O'Keefe discovered.
"I remember how great was the scoffing in the early 1970s when John first described 'place cells'," said John Stein, emeritus professor of physiology at Oxford University.
"'Bound to be an artifact', 'He clearly underestimates rats' sense of smell' were typical reactions. Now, like so many ideas that were at first highly controversial, people say: 'Well that's obvious'!"
O'Keefe's work, in turn, inspired the Moser husband-and-wife team, for whom he became a mentor.
In 2005, they discovered a new type of cell in an area of the brain next to the hippocampus called the entorhinal cortex.
These cells fired in an astonishing hexagonal pattern as the rat passed multiple locations enticed by chocolate treats, and the couple concluded that they functioned as a coordinate system for spatial navigation.
"Place" and "grid" cells have since been found in mammals other than rats, and evidence points to them also existing in humans. Some early research suggests the "grid" system is fully established in infants by about three or four weeks after birth.
If so, it would mean that babies are born with a very powerful, if primitive sense of where they are in space -- a sense that becomes fine-tuned as their minds adapt to the world.
The work opens a door to advancing fundamental understanding of how the mind works, and may explain why memories of events often have associations with particular places.
Another benefit could be a better understanding of what causes Alzheimer's disease. One of its early symptoms is not recognising a familiar environment, and getting lost or wandering off.
"When we understand how the (location and navigation) system works, we will understand why it doesn't," Laure Rondi-Reig of the neuroscience department at France's National Centre for Scientific Research told AFP.
"By asking the big questions in biology, we can continue to deliver insights into relevant and pressing issues such as those presented by dementia and Alzheimer’s disease," added Mark Downs, chief executive of the London-based Society of Biology.