Where am I? Scientists win Nobel for putting us in place, on the grid

Understanding where we're located may seem trivial, but it has a profound effect on life. We strongly associate memories with specific locations, and we can retain the ability to navigate between places for decades. A sense of location is also associated with basic survival: you can remember where to go next to get food, or know that approaching an edge should be done cautiously if you recall that you're 300 meters up a mountainside.

All of which suggests that producing a sense of place—and relating that sense to both memories and to other locations—should be central to the lives of complex animals. But until the 1970s, we had very little idea of how this knowledge was generated and retained by the brain. This year, the Nobel Prize committee is honoring three researchers for their roles in figuring out "the brain's GPS."

A sense of place

One half of the prize is going to John O’Keefe, an American who has worked at the University College, London for decades. O’Keefe's work took advantage of technological developments in the late 1960s. At the time, researchers had known for a while how to record the activity of individual neurons in the brain, but this was extremely invasive and generally done on anesthetized animals. A key breakthrough was the miniaturization of the equipment, which was eventually made small enough that the rats could be monitored while they were awake and active.

O’Keefe let the rats be extremely active, allowing them to explore an unfamiliar environment while having individual neurons under constant observation. He focused his monitoring on the hippocampus, a portion of the brain that's heavily involved in the use of memory. Unexpectedly, he found a region that contained neurons only active when the rats were in specific parts of the enclosure. Those neurons, called "place neurons," can work in combination; different groups can fire at different locations within an area, provide a complete map of the area, provide information on how different locations are linked, and ensure that the appropriate memories are associated with locations.

Although O'Keefe's findings weren't met with immediate, universal acceptance, having a basic handle on how location was handled opened the door to a huge number of further studies. People quickly went to work figuring out how sensory input—the sights and smells of a place—helped inform the place neurons as to when they should fire. Other work focused on how the firing of place neurons allowed the rats to trigger memories associated with that place.

On the grid

The latter category of work was taken up by the husband-and-wife team of Edvard and May-Britt Moser. Now both directors of institutes in their native Norway, the Mosers spent time in several labs early in their careers, including O'Keefe's. They started focusing on a brain region called the entorhinal cortex that's connected to the hippocampus, where the place neurons live.

Again, allowing rats to explore a large enclosure while monitored was key; the Mosers discovered that the entorhinal cortex contains what are called "grid cells." The concept of grid cells will be familiar to anyone who's played games such as Settlers of Catan that involve a hex map. Whenever an animal was within a specific hexagonal area of the enclosure, its corresponding grid cells fired. Put in the terms used by the Nobel committee materials, the grid cells "were active in multiple places in the open box that together formed nodes of an extended hexagonal grid."

Combined, the two systems—place neurons and grid cells—provide a complete map of an area. While the grid cells provide fine-scaled spatial relationships within the area, place neurons take areas of the grid and assign them meaning by associating them with memories of environmental cues and experiences. The system's role in ordering spatial locations can affect memory more generally, given that we can sometimes order experiences in our past based on where they occurred.

Confirming the role of these cells in memory, researchers have watched groups of place neurons replay a sleeping animal's earlier activity—a key step in consolidating memories. And as you'd expect from such an essential system, the dual place/grid cell system appears to be present in all mammals studied, including humans.