Nobel Prize in Physiology or Medicine 2014: Place Cells, Grid Cells and the Brain's Inner GPS

This note covers the Nobel Prize in Physiology or Medicine 2014: who won it, how place cells and grid cells in the brain form an "inner GPS" for navigation, how the discovery unfolded across more than three decades, why it matters for memory and for diseases such as Alzheimer's, and quick facts for exams.

What was the Nobel Prize in Physiology or Medicine 2014 awarded for?

The Nobel Prize in Physiology or Medicine 2014 was awarded "for their discoveries of cells that constitute a positioning system in the brain". This is the official citation, and it was shared between three scientists working on the same broad question.

In plain words, the laureates found that the brain contains specialised nerve cells that work together like a built-in satellite navigation system.

Just as a GPS device in a car uses satellite signals to tell you where you are and helps you plan a route, certain brain cells fire in patterns that tell an animal (or a person) where it is in space and help it find its way from one place to another. The committee called this an "inner GPS".

The prize's full official name is the Nobel Prize in Physiology or Medicine, awarded each year by the Nobel Assembly at Karolinska Institutet in Stockholm.

In 2014 it recognised work that answered a question philosophers and scientists had asked for centuries: how does the brain build an internal map of the space around us, and how do we use that map to navigate?

Who are the laureates?

John O'Keefe

John O'Keefe was born on 18 November 1939 in New York, NY, USA. At the time of the award he was affiliated with University College, London, United Kingdom. He received one half of the prize.

O'Keefe trained in physiological psychology at McGill University in Canada, earning his doctorate in 1967, before moving to University College London for postdoctoral work.

He later became Professor of Cognitive Neuroscience there in 1987, and at the time of writing he is director of the Sainsbury Wellcome Centre for Neural Circuits and Behaviour at University College London.

His key contribution was the 1971 discovery of place cells in the hippocampus, a brain region that lies deep in the centre of the brain.

May-Britt Moser

May-Britt Moser was born on 4 January 1963 in Fosnavåg, Norway. At the time of the award she was affiliated with the Norwegian University of Science and Technology (NTNU), Trondheim, Norway. She received one quarter of the prize.

She studied psychology at the University of Oslo, where she met her future husband and co-laureate Edvard I. Moser, and completed a PhD in neurophysiology in 1995.

After a postdoctoral fellowship at the University of Edinburgh and a spell as a visiting scientist at University College London, she moved to NTNU in Trondheim in 1996, becoming Professor of Neuroscience in 2000. She directs the Centre for Neural Computation in Trondheim. With Edvard Moser, she co-discovered grid cells in 2005.

Edvard I. Moser

Edvard I. Moser was born on 27 April 1962 in Ålesund, Norway. At the time of the award he was also affiliated with NTNU, Trondheim, Norway. He received one quarter of the prize.

He too studied at the University of Oslo and gained his PhD in neurophysiology in 1995, following a similar path through Edinburgh and London before the couple settled at NTNU in 1996.

He became Professor there in 1998 and currently directs the Kavli Institute for Systems Neuroscience in Trondheim. Together with May-Britt Moser, he identified grid cells in the entorhinal cortex, a brain area next to the hippocampus.

What problem were they trying to solve?

Why do we need a sense of place?

Knowing where you are and being able to navigate are among the most basic things a brain does.

Humans and animals constantly need to know where they are, remember how they got there, and work out how to get somewhere else.

This "sense of place" is linked to a "sense of distance", which depends on tracking movement and recalling earlier positions.

What did earlier thinkers propose?

Philosophers had wondered about this long before neuroscience existed. Long before modern neuroscience, the German philosopher Immanuel Kant proposed that certain mental abilities, including the idea of space, are inherent to the mind rather than learned purely from experience. He treated the perception of place as an inbuilt principle through which a person has to organise and understand the surrounding world.

In the mid-20th century, the American psychologist Edward Tolman studied rats running through maze-like labyrinths and proposed that they form a cognitive map of their surroundings in the brain, which lets them find their way and choose the best path. His view went against the then-common idea that complex behaviour is just a chain of automatic responses to sensory signals.

But Tolman's idea stayed theoretical: nobody knew which cells in the brain, if any, actually built such a map, or how a map-like idea of space could be represented by nerve cells at all.

What finally made the experiments possible?

This was the gap the three laureates filled. Their experiments became possible once scientists developed ways to record the electrical activity of single nerve cells using tiny implanted wires in animals that were moving about naturally, rather than being restrained or tested in a fixed stimulus-response set-up. This let the laureates watch brain cells at work during ordinary behaviour, and finally locate the cognitive map inside real brain tissue, showing how it is built and used.

How do place cells work?

What did O'Keefe discover in the hippocampus?

In the late 1960s, O'Keefe began recording electrical signals from single nerve cells in the hippocampus of rats that were moving freely around a room, rather than being restrained. He had moved to University College London to work in a pain-research laboratory, before turning to study how the brain controls behaviour.

In 1971, together with Jonathan Dostrovsky, he discovered that certain cells in a part of the hippocampus called CA1 fired only when the rat was in one particular spot, its place field; when the animal moved elsewhere, different cells took over. He called these place cells.

How did O'Keefe show this was a map, not just raw vision?

O'Keefe systematically changed the room and tested different explanations, and showed that place cells were not simply reacting to what the rat could see; a cell's firing represented a more abstract, internal sense of location, built up from a combination of cues rather than one single sensory signal.

Different combinations of active place cells corresponded to different environments, so the hippocampus could, in effect, store many separate maps. A specific pattern of place cell activity could even serve as a kind of memory trace for a particular environment, since O'Keefe and Lynn Nadel later proposed that the hippocampus gives the brain a spatial reference map, or sense of place.

O'Keefe also found that when many place cells rearrange together as an animal is moved into a new setting, a process he called remapping, this rearrangement is learned and, once it settles, can stay stable over a long time. This suggested that place cells can act as a cellular basis for storing memories of particular environments, not just for reading out current position.

1. A rat explores a bounded space such as an open box or room.
2. Microelectrodes record electrical firing from individual nerve cells in the hippocampus.
3. Each place cell is found to fire only when the rat occupies one specific location, called its place field.
4. Different place cells have different place fields, so together they tile the whole environment.
5. The overall pattern of which place cells are active at a given moment represents the rat's position, and a different, learned combination represents a different, remembered environment.

Draw a square representing an open field with a rat moving inside it.

Mark several separate clusters of dots, each cluster in a different corner or region, with each cluster shown in its own colour to represent one place cell firing only when the rat is in that particular patch.

Definition: Place cell. A nerve cell in the hippocampus that becomes active only when an animal is in one particular location within its environment.

How do grid cells and the wider navigation system work?

Through the 1980s and 1990s most scientists thought that place fields were produced entirely inside the hippocampus itself. May-Britt Moser and Edvard Moser, who had both trained in Per Andersen's laboratory in Oslo and later worked as visiting scientists in Edinburgh and in O'Keefe's own laboratory in London, asked whether place cell firing instead depended on signals arriving from elsewhere in the brain.

They focused on the entorhinal cortex, the structure that sends the main input into the hippocampus. By 2004 the Mosers had already found cells there sharing some properties with hippocampal place cells. Then, in 2005, using larger spaces for the animals to explore, they found a completely new type of cell with an unexpected firing pattern.

Certain cells there fired whenever the rat passed through a set of locations arranged in a repeating hexagonal grid across the whole room, somewhat like the hexagonal cells of a honeycomb. The Mosers named these grid cells.

Each grid cell has its own grid pattern, slightly shifted from its neighbours but sharing the same spacing and orientation within a given part of the entorhinal cortex, and together a population of grid cells can cover every point in an environment. The Mosers later found that grid spacing varies across the entorhinal cortex, with the largest grids found towards one end of the structure, and that cells are organised into functional groups, or modules, with grid sizes ranging from a few centimetres up to several metres, so that both small and large spaces can be covered.

The Mosers showed that this hexagonal firing pattern was not simply imported from something in the room; it was generated by the brain's own internal circuitry, acting as a coordinate system that lets the animal measure distance and direction as it moves, a process called path integration.

The entorhinal cortex also contains other spatially tuned cells: head-direction cells, first described in a nearby brain structure by James Ranck, which act like an internal compass and fire according to which way the head is pointing, and border cells, which fire in relation to the walls of an enclosed space and whose existence O'Keefe and colleagues had earlier predicted from theoretical modelling.

The Mosers' later work showed that grid cells, head-direction cells and border cells are wired together and feed into the place cells of the hippocampus, forming one connected circuit in which information can flow in both directions between the entorhinal cortex and the hippocampus.

Draw a large square arena and mark the locations where one grid cell fires as a set of dots forming the corners of repeating equilateral triangles, so the overall pattern looks like a honeycomb of hexagons spread evenly across the whole square.

In 1971, together with Jonathan Dostrovsky, he discovered that certain cells in a part of the hippocampus called CA1 fired only when the rat was in one particular spot; when the animal moved elsewhere, different cells took over. He called these place cells.

O'Keefe showed that place cells were not simply reacting to what the rat could see; a cell's firing represented a more abstract, internal sense of location.

Different combinations of active place cells corresponded to different environments, so the hippocampus could, in effect, store many separate maps. A specific pattern of place cell activity could even serve as a kind of memory trace for a particular environment.

1. A rat explores a bounded space such as an open box or room.
2. Microelectrodes record electrical firing from individual nerve cells in the hippocampus.
3. Each place cell is found to fire only when the rat occupies one specific location, called its place field.
4. Different place cells have different place fields, so together they tile the whole environment.
5. The overall pattern of which place cells are active at a given moment represents the rat's position, and a different combination represents a different, remembered environment.

Draw a square representing an open field with a rat moving inside it.

Mark several separate clusters of dots, each cluster in a different corner or region, with each cluster shown in its own colour to represent one place cell firing only when the rat is in that particular patch.

Definition: Place cell. A nerve cell in the hippocampus that becomes active only when an animal is in one particular location within its environment.

How do grid cells and the wider navigation system work?

More than three decades after O'Keefe's discovery, in 2005, May-Britt Moser and Edvard Moser were studying the connections feeding into the hippocampus when they found an unexpected pattern of activity in a nearby region called the entorhinal cortex.

Certain cells there fired whenever the rat passed through a set of locations arranged in a repeating hexagonal grid across the whole room, somewhat like the hexagonal cells of a honeycomb. The Mosers named these grid cells.

Each grid cell has its own grid pattern, slightly shifted from its neighbours, and together a population of grid cells can cover every point in an environment.

The Mosers showed that this hexagonal firing pattern was not simply imported from something in the room; it was generated by the brain's own internal circuitry, acting as a coordinate system that lets the animal measure distance and direction as it moves, a process called path integration.

The entorhinal cortex also contains other spatially tuned cells: head-direction cells, first described in a nearby brain structure by James Ranck, which act like an internal compass and fire according to which way the head is pointing, and border cells, which fire in relation to the walls of an enclosed space and whose existence O'Keefe and colleagues had earlier predicted from theoretical modelling.

The Mosers' later work showed that grid cells, head-direction cells and border cells are wired together and feed into the place cells of the hippocampus, forming one connected circuit.

Draw a large square arena and mark the locations where one grid cell fires as a set of dots forming the corners of repeating equilateral triangles, so the overall pattern looks like a honeycomb of hexagons spread evenly across the whole square.

How did the discovery unfold?

The work stretched across more than three decades, moving from a single new type of cell found in rats to a full picture of a brain-wide positioning system, later confirmed in several other mammals including humans.

Why does it matter?

Why was this a "paradigm shift"?

The discovery of place cells and grid cells answered a question that had puzzled philosophers and scientists for a very long time: how does the brain build a map of space and use it to navigate? The Nobel committee described this as showing a "paradigm shift" in how groups of specialised cells together carry out complex mental functions.

The findings have been confirmed in several other mammals, and later studies using brain imaging and recordings from patients undergoing surgery suggest that humans too have place-like and grid-like cells in the hippocampus and entorhinal cortex.

What does it mean for Alzheimer's disease?

This matters for medicine because the hippocampus and entorhinal cortex are often among the first brain regions affected in Alzheimer's disease, and patients with this disease frequently lose their way and fail to recognise familiar surroundings. Researchers working with a mouse model of Alzheimer's disease found that the breakdown of place-cell firing patterns matched the worsening of the animals' spatial memory.

Understanding the brain's positioning system may help explain why this kind of spatial memory loss happens, although there is no immediate way yet to turn this research into a cure or clinical treatment; brain disorders remain a leading cause of disability with few effective treatments overall.

What wider questions does this open up?

The work has also opened up broader research into how the brain handles memory, planning and thinking, since place cells appear to do more than just mark location: evidence suggests they can also be involved in remembering sequences of past and future places, which may relate to how we store personal, time-ordered memories of events, and how such memories are consolidated during sleep.

More widely, the similarity of hippocampal and entorhinal structures across many mammal species, and even in some non-mammal vertebrates with navigational ability, suggests that this place-and-grid system may be a very old and widely shared solution to the problem of finding one's way through the world.

How does this connect to what you study?

Why does this matter for biology students?

This discovery links directly to the nervous system and the brain, topics covered in school biology.

Place cells and grid cells are part of the hippocampus and entorhinal cortex, structures that sit within the wider nervous system studied alongside neurons, synapses and reflex actions.

The idea that memory can be stored as a pattern of nerve-cell activity also connects to broader lessons on how the brain learns and remembers.

It is also a good example, for general-studies and science exams, of how a basic question (how do we know where we are?) can be investigated using careful experimental methods, in this case recording electrical signals from single nerve cells in animals that are free to move naturally rather than restrained.

What do place and grid cells reveal about memory and the human brain?

The laureates' discoveries did more than explain navigation; they also opened a window onto how the brain stores memories of events and places.

What did the case of patient HM show?

Decades earlier, a patient known by the initials HM had both hippocampi surgically removed to treat severe epilepsy, and afterwards lost the ability to form new memories while still recalling old ones. This showed that the hippocampus was essential for a kind of memory later called episodic memory, the ability to remember events a person has personally experienced.

How do place cells relate to memory and sleep?

Place cells do not only mark where an animal is right now. Later research found that they can also carry information about where the animal has just been and where it is heading next, which may help explain how the brain keeps a time-ordered record of events, similar to episodic memory.

Recordings made while animals sleep have shown that place cells which fired in a particular sequence while the animal explored a route tend to fire again in the same sequence during later sleep. This kind of replay is thought to help consolidate, or firmly store, memories of a spatial route after the original experience.

What evidence is there in the human brain?

Separate studies of human brains have supported the idea that people have a similar system. Recordings taken from the brains of patients with epilepsy who were undergoing surgery, as well as brain-imaging studies, have found place-like cells in the human hippocampus and grid-like cells in the human entorhinal cortex.

In one well-known study, researchers found that the hippocampus of London taxi drivers, who spent a year-long training period learning the layout of thousands of streets without using a map, grew larger over that training, and ended up bigger on average than in people who had not done this training. This supported the idea that the hippocampus is closely tied to building and using detailed spatial knowledge.

Quick facts for exams

The Nobel Prize in Physiology or Medicine 2014 was announced on 6 October 2014 by the Nobel Assembly at Karolinska Institutet. It was shared between John O'Keefe (one half) of University College London, and May-Britt Moser and Edvard I. Moser (one quarter each) of the Norwegian University of Science and Technology, Trondheim. The citation honoured their discoveries of cells forming a positioning system, or "inner GPS", in the brain.

O'Keefe found hippocampal place cells in 1971; the Mosers found entorhinal grid cells in 2005. Together these cells help animals and humans know where they are and find their way.

Note: Source. The prize facts in this note are from the Nobel Prize's official site, nobelprize.org.

Glossary

• Hippocampus — a region deep in the centre of the brain, important for memory and for sensing location.
• Entorhinal cortex — a brain region next to the hippocampus, where grid cells, head-direction cells and border cells are found.
• Place cell — a hippocampal nerve cell that fires only when an animal is in one specific location.
• Grid cell — an entorhinal nerve cell that fires at multiple locations arranged in a repeating hexagonal pattern.
• Head-direction cell — a nerve cell that fires according to which direction the head is currently pointing.
• Border cell — a nerve cell that fires in relation to the walls or edges of an enclosed space.
• Cognitive map — an internal mental representation of an environment, proposed by Edward Tolman, that allows navigation.
• Inner GPS — the Nobel committee's description of the brain's combined positioning system of place, grid, head-direction and border cells.
• Path integration — the process of tracking one's own movement (distance and direction) to update a sense of position.
• Episodic memory — the ability to remember personally experienced events, linked to hippocampal function.
• Remapping — a change in which combination of place cells is active when an animal is in a different environment.
• Microelectrode recording — a technique for recording electrical activity from individual nerve cells, used in freely moving animals.

Common errors and misconceptions

• Misconception: Place cells and grid cells are the same thing. Correct: Place cells are in the hippocampus and signal a single location; grid cells are in the entorhinal cortex and provide a coordinate system across many locations.
• Misconception: The whole prize was awarded for one single discovery made at one time. Correct: O'Keefe discovered place cells in 1971, and the Mosers discovered grid cells separately in 2005, more than three decades later.
• Misconception: The "inner GPS" is only found in rats. Correct: Later studies found evidence of place-like and grid-like cells in humans and other mammals too.
• Misconception: The three laureates worked as one team throughout. Correct: O'Keefe worked independently in London; the Mosers, a married couple, later trained partly in O'Keefe's own laboratory before making their separate discovery in Trondheim.
• Misconception: This discovery has already produced a cure for Alzheimer's disease. Correct: There is no immediate translation of these findings into clinical treatment, though they may help explain the spatial memory loss seen in the disease.
• Misconception: Grid cells fire randomly across the environment. Correct: Grid cells fire in a precise, repeating hexagonal pattern that covers the whole space evenly.

Exam-style questions with model answers

Q1. In which brain region did John O'Keefe discover place cells? [1 mark]

1. John O'Keefe discovered place cells in the hippocampus, a region deep in the centre of the brain.

Q2. State the official citation for the Nobel Prize in Physiology or Medicine 2014. [2 marks]

1. The citation reads "for their discoveries of cells that constitute a positioning system in the brain".
2. The prize was divided, with one half to John O'Keefe and the other half jointly to May-Britt Moser and Edvard I. Moser.

Q3. Explain what grid cells are and where they are located. [4 marks]

1. Grid cells are nerve cells found in the entorhinal cortex, a brain region next to the hippocampus.
2. Each grid cell fires not at one place but at multiple locations in an environment.
3. These firing locations form a repeating hexagonal pattern across the whole space, similar to a honeycomb.
4. This pattern provides the brain with an internal coordinate system that supports precise positioning and path integration during navigation.

Q4. Why did the Nobel committee describe this discovery as a "paradigm shift"? [4 marks]

1. Before this work, nobody had located a physical cellular basis for the brain's internal map of space.
2. O'Keefe's place cells showed that single nerve cells could represent an abstract idea such as location, not just raw sensory input.
3. The Mosers' grid cells showed that the brain can generate its own internal coordinate system rather than simply copying features of the outside world.
4. Together these findings showed how groups of specialised cells cooperate to produce a higher cognitive function, changing how scientists understand complex brain functions generally.

Q5. Describe how the brain's positioning system works and discuss its relevance to human disease. [6 marks]

1. Place cells in the hippocampus each fire when an animal is at one particular location, and different combinations of active place cells represent different remembered environments.
2. Grid cells in the entorhinal cortex fire in a repeating hexagonal pattern, giving the brain a coordinate system to measure distance and direction as the animal moves, a process called path integration.
3. Head-direction cells act like an internal compass, while border cells respond to the walls of an enclosed space; these, together with grid cells, feed into the hippocampal place cells, forming one connected circuit, the "inner GPS".
4. Studies using brain imaging and recordings in patients suggest humans have similar place-like and grid-like cells.
5. Because the hippocampus and entorhinal cortex are among the first regions affected in Alzheimer's disease, patients with the disease often lose their way and fail to recognise familiar places.
6. Understanding this positioning system may help explain such spatial memory loss, although there is no immediate way yet to translate this understanding into a clinical cure.

Q6. Name the universities where each laureate was affiliated at the time of the award. [2 marks]

1. John O'Keefe was at University College, London.
2. May-Britt Moser and Edvard I. Moser were both at the Norwegian University of Science and Technology (NTNU), Trondheim.

Q7. What historical idea did the discovery of place cells help confirm, and who had proposed it earlier? [3 marks]

1. Place cells gave physical evidence for the idea of a "cognitive map" in the brain.
2. This idea had been proposed earlier by the American psychologist Edward Tolman, based on studies of rats learning to navigate mazes.
3. O'Keefe's discovery of place cells showed, for the first time, a cellular location in the brain where such a map could actually be represented.

Q8. What share of the prize did each laureate receive, and why might the shares differ? [2 marks]

1. John O'Keefe received one half of the prize, while May-Britt Moser and Edvard I. Moser each received one quarter.
2. The shares differ because O'Keefe's discovery of place cells and the Mosers' joint discovery of grid cells were treated as two separate contributions.

Key takeaways

• The 2014 Nobel Prize in Physiology or Medicine honoured the discovery of the brain's "inner GPS", or positioning system.
• John O'Keefe discovered hippocampal place cells in 1971, each firing at one specific location.
• May-Britt Moser and Edvard I. Moser discovered entorhinal grid cells in 2005, firing in a hexagonal pattern across space.
• Head-direction cells and border cells, also in the entorhinal cortex, work alongside grid cells and feed into place cells.
• The discovery answered a centuries-old question about how the brain builds an internal map of space.
• Later evidence suggests humans also have place-like and grid-like cells, not just rats.
• The hippocampus and entorhinal cortex are often affected early in Alzheimer's disease, which may explain why patients lose their way.
• The prize was shared, with O'Keefe receiving one half and the Mosers one quarter each.

Test yourself

Where did John O'Keefe discover place cells, and in which year?

John O'Keefe discovered place cells in the hippocampus of freely moving rats in 1971.

What shape pattern do grid cells form when they fire?

Grid cells fire at multiple locations arranged in a repeating hexagonal pattern, similar to a honeycomb, across the whole environment.

Where were May-Britt Moser and Edvard I. Moser based at the time of the award?

They were both affiliated with the Norwegian University of Science and Technology (NTNU) in Trondheim, Norway.

What phrase did the Nobel committee use to describe the brain's positioning system?

The committee described it as an "inner GPS" that allows orientation and navigation in space.

Which philosopher argued that the concept of space is built into the mind?

The German philosopher Immanuel Kant argued that the perception of space exists as an innate, inbuilt mental ability.

Why might this discovery matter for Alzheimer's disease research?

The hippocampus and entorhinal cortex are often affected early in Alzheimer's disease, which may help explain why patients lose their sense of place.

How many daughters do Edvard and May-Britt Moser have, and where did they both train before Trondheim?

They have two daughters, and both trained at the University of Edinburgh and University College London before moving to Trondheim.