Their discoveries in the brain have solved the puzzles that have plagued philosophers for centuries

▎Where am I editing by WuXi AppTec's content team? Where am i going? How do I remember the road so that I can go to the same place next time? The problems of sense of orientation and navigation capabilities have long plagued philosophers and scientists
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More than 200 years ago, German philosopher Immanuel Kant argued that certain mental abilities exist as prior knowledge, independent of experience
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He believes that the concept of space is a built-in principle of the mind, and we must perceive the world through this built-in principle
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Later, behavioral psychologists proposed that the understanding of the external environment in the mind will form a "cognitive map" for animals to find their way
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In the end, neuroscientists have spanned decades of "relay" and revealed the answer to this question: They discovered and determined a set of positioning and navigation systems composed of different nerve cells in the brain.
It is this set of "built-in GPS" that allows the brain to create A map that recognizes the surrounding environment allows us to navigate for ourselves in a complex environment
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In 2014, three discoverers of the "built-in GPS" in the brain were awarded the Nobel Prize in Physiology or Medicine
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▲The 2014 Nobel Prize in Physiology or Medicine was shared by three neuroscientists.
Among them, Professor John O'Keefe won 1/2 of the award, and Professor May-Britt Moser and Professor Edvard I.
Moser shared 1/2 of the award (picture Source: https:// Credit: Nobel Media AB.
Photo: A.
Mahmoud) "The seahorse map is continuing to navigate you" In 1970, John O'Keefe started The study of the hippocampus of the brain
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At McGill University in Canada, where he was studying for his Ph.
D.
, scientists from the Department of Psychology had already begun a more than ten-year study of Henry Molaison (referred to as HM), a famous patient with amnesia.
Research
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They confirmed that Henry could no longer form new memories of daily life and recall specific episodes of his past experiences after he had undergone surgery to remove both medial temporal lobes (including the hippocampus and its surrounding structures)
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Therefore, the importance of the hippocampus to memory has attracted worldwide attention
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O'Keefe came to University College London, UK, using the newly developed technology, began to work with graduate student Jonathan Dostrovsky to record nerve cell signals in the hippocampus of rats with electrodes
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The anatomical structure of the hippocampus of rats is very similar to that of humans, and scientists hope to gain insights into how memories are stored and retrieved
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▲Schematic diagram of the brain structures of humans and mice (picture source: reference [2]) For several months, they observed various natural behaviors of animals when they were moving freely, while monitoring the electrical activities of various nerve cells in the hippocampus
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In this process, the firing pattern of a type of cell is relatively "quiet" and completely unexpected
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These nerve cells will suddenly start to become active at irregular intervals, and it seems that there is no correlation to the animal's behavior
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Suddenly one day, when recording a beautiful nerve cell, O'Keefe ushered in his moment of inspiration: "I realized that these cells are not interested in what animals are doing or why they are doing.
They are interested in animals.
Position in the environment!" They called the recorded cells a place cell, which represented different positions in the environment
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The activities of cells in different locations are combined to create an internal map that represents a specific environment
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▲The picture on the left depicts the movement trajectory of the rat in the clearing.
When the animal reaches a specific position, the cells in the hippocampus (the position shown in the color on the right) send out a high-speed discharge signal (picture source: reference [1]) at O' It seems to Keefe that now they may have found the neural basis for Kant's a priori sense of space
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Soon, in a short three-page paper published in 1971, O'Keefe summarized their findings
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He wrote: "These findings indicate that the hippocampus provides a spatial reference map for the rest of the brain
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Without this map, animals cannot know how to get from a location in the environment by any specific route to a specific location.
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.
" In addition to discovering the existence of location cells, O'Keefe has some speculations about the features and functions of this cognitive map
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For example, animals can move in the environment in a flexible way.
In addition to a set of information that represents their current location, the brain should also be able to calculate and predict their location based on environmental information and the distance, direction, and speed of movement, just like an airplane The technology used in the navigation system is like that
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In addition, how hippocampal lesions affect animal behavior can now be explained
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At first, these thoughts and speculations were just a brief review article
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But with the collection and sorting of the literature, the manuscripts of O'Keefe and collaborator Dr.
Lynn Nadel reached several hundred pages in the second year
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In the end, after six years of writing and editing, they published a monograph "The Hippocampus as a Cognitive Map", which covered almost all important documents related to the hippocampus at that time, and tried to put their ideas in the relevant In the historical background of the philosophy and psychology of the sense of space
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▲"Hippocampus as a Cognitive Map" published by Oxford University Press.
The picture on the right shows the two authors (picture source: reference [2]).
In this monograph, two scientists also created a poem description The sense of space is important
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Space participates in all our actions
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We live in it, walk in it, we explore it, and we keep it
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It is always easy for us to point out some fragments of space: such as this room, such as the sky, such as the gap between two fingers, such as the open space left after the piano is finally moved away
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The Labyrinth in the Water In "The Hippocampus as a Cognitive Map", O'Keefe made many pioneering predictions on how the hippocampus participates in space navigation.
Many of these predictions exceed the data available at the time and inevitably suffer Some doubts came
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Dr.
Richard Morris at the University of St Andrews in Scotland was one of the first scientists to test O'Keefe's predictions through experiments
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In order to test the spatial memory of animals, Morris designed a swimming pool ingeniously
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This swimming pool is filled with opaque liquid (usually water mixed with milk).
After entering the pool, rats cannot directly see the sunken escape platform hidden in the water.
Only after swimming around can they find the platform and climb on it to rest
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Animals with normal navigation ability can learn to reach the platform in the shortest path according to the clues of the room outside the pool after several trainings
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However, rats with damaged hippocampus have difficulty finding an underwater platform, indicating that the brain's built-in navigation system is malfunctioning
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The water maze designed by Morris is simple but powerful, and it has proved to be an extremely valuable method to test the function of the hippocampus
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Today, the Morris water maze, named after him, is one of the most widely used behavioral tests in neuroscience
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▲Professor Richard Morris and the water maze he invented (picture source: Reference [3]) were at the University of Oslo in Norway.
On this day, two young students walked out with Richard Morris’s paper on the water maze.
The office of neuroscientist Professor Per Andersen
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The two students are studying in the Department of Psychology, but they want to change their careers and follow Professor Anderson to study the mechanism of memory formation from the perspective of nerve cells
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There are many people who want to enter the Anderson laboratory.
The professor told them that if they can successfully create the Morris water maze introduced in this thesis, they agree to accept them into the laboratory to do a master's degree thesis
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The two young people quickly completed the challenge with their strong hands-on ability.
In the next few months, they began to study the relationship between hippocampal damage and memory deficits using a water maze
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These two people are the Moser couple, May-Britt Moser and Edvard I.
Moser, the other two winners of the 2014 Nobel Prize in Physiology or Medicine
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The Moser couple in the entorhinal cortex outside the hippocampus stayed in Andersen's laboratory for several years.
After finishing their master's thesis, they continued to complete their doctoral thesis
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Later, after Morris’ introduction, Edvard I.
Moser and May-Britt Moser came to John O’Keefe’s laboratory at University College London to learn how to use implanted electrodes to capture the activity of individual brain neurons in freely moving animals.
They want to use this technique to explore whether neural activity outside of the hippocampus can guide local cells to fire
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Their eyes focused on a structure called the entorhinal cortex
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This structure is close to the hippocampus and is located on the dorsal edge of the rat brain.
Most of the output signal enters the dentate gyrus of the hippocampus, then connects to the CA3 of the hippocampus, and then to the CA1 of the dorsal hippocampus, which is O'Keefe.
The place where the location cell was first discovered
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Inside the entorhinal cortex, the Moser couple found that some of these cells have the same characteristics as the hippocampal cells, and they will fire when the animal moves to a specific location
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Later, when they adjusted the experiment to allow the animals to run around in a more open space, a new cell type in the entorhinal cortex attracted their attention
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The activity characteristics of these cells are extremely unusual: a cell is activated when the animal passes through multiple locations, and the coordinates of these locations combine to present a highly symmetrical hexagonal grid
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In the past, no one has ever seen a grid pattern in any other brain cell
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So, more than thirty years after O'Keefe discovered the location cells, the Moser couple discovered another key component of the brain’s built-in navigation system in 2005: grid cells
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▲The grid cells in the entorhinal cortex (the blue indicator on the right) send out electric signals when the rat passes through the nodes of the hexagonal grid (picture source: reference [1]) After various tests, the Moser and his wife gradually interpreted The mode of action of the grid cells is shown
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They found that each grid cell in the entorhinal cortex forms a unique coordinate system, and the discharge pattern follows a specific grid spacing and orientation; while the grid cells in different regions have different grid spacings, ranging from a few centimeters to a few centimeters.
It varies from a few meters
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In this way, grid cells can cover every point in various environments, and can also measure the distance between different points in space
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In addition to the location cells discovered by O'Keefe and the grid cells discovered by the Moser couple, the scientists also discovered other cells involved in the creation of cognitive maps
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For example, James Ranck first described head direction cells in 1985.
They are like compasses that become active when the animal's head is facing a certain direction
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Some scientists have also found the border cells predicted by O'Keefe with theoretical models.
These cells will become active when the animal walks to a border such as a wall in a closed environment
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In subsequent experiments, the Moser couple further explored the relationship between various types of cells
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They showed that the entorhinal cortex is like the computing center that characterizes the sense of space.
The grid cells are embedded in the network from the head to the cells and the border cells.
In many cases, they have a combined function.
They project to the hippocampus location cells to realize positioning together.
And navigation
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Positioning and navigation systems in the human brain Although location cells and grid cells were originally found in rodent brains, with the application of brain imaging technology and research on patients undergoing neurosurgery, in the last ten years Scientists have also successively discovered position cells and grid cell systems in the brains of humans and other mammals
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Moreover, the structural similarity between hippocampus and entorhinal cortex in different animals indicates that this set of positioning and navigation systems in the brain may be conserved in the evolution of spinal animals
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In patients with Alzheimer's disease, the hippocampus and entorhinal cortex are often affected early in the onset of the disease, and a common manifestation of these patients is disorientation and inability to recognize the environment
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Understanding the positioning and navigation systems in the human brain will help us understand why patients with this disease have a devastating loss of spatial memory
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The official report of the Nobel Prize pointed out that the discovery of the brain positioning and navigation system represents a paradigm shift.
We have a new understanding of how the collection of specialized cells work together to perform higher cognitive functions, and to understand other cognitions.
Processes such as memory, thinking, and planning open up new avenues
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 Reference: [1] The Nobel Prize in Physiology or Medicine 2014.
NobelPrize.
org.
Nobel Prize Outreach AB 2021.
Mon.
30 Aug 2021.
https:// 2] John O'Keefe (2014) Spatial Cells in the Hippocampal Formation.
Nobel Lecture.
https:// Brain Prize goes to Richard Morris for memory research.
Retrieved Sep.
14, 2021 from https://