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Imagine that

THE WASHINGTON POST – The Scottish philosopher David Hume said that “men are mightily governed by the imagination”. So too is the humble rat, according to research published last week in the journal Science.

Nearly a decade of work culminated in an extraordinary set of experiments in which researchers at Howard Hughes Medical Institute placed rats into a virtual reality arena that provided them with the Jedi-like power to “teleport” themselves or an object to a specific place using only their thoughts.

Authors of the paper said future studies of this kind could lead to the discovery of methods that will help to restore or enhance brain functions by understanding a person’s intentions, and perhaps could broaden our understanding of the memory-loss condition amnesia.

The work built on previous scientific discoveries revealing that deep in the brain animals and humans have their own GPS system. Found in the hippocampus, a region that plays a major role in memory and imagination, this internal GPS system translates places and events into patterns of neurons firing, a sign that the brain cells are communicating. Those patterns are then stored in the brain and used to navigate the everyday world.

The specialised cells that do the work, known as place and grid cells, serve as crucial building blocks that allow us to remember the past and imagine the future. The three scientists who discovered the cells were awarded the 2014 Nobel Prize in physiology or medicine for revealing functions that “are fundamental to our existence”.

“We can lie in bed at night, close our eyes and put ourselves in the past or the future,” said lead author of the new paper and a postdoctoral fellow for the Howard Hughes Medical Institute Chongxi Lai who is now based at Beth Israel Deaconess Medical Center in Boston.

PHOTO: FREEPIK
PHOTO: FREEPIK

Imagination is critical to innovation, Lai continued. “Any invention happens twice – in the inventor’s mind, then in the real world.”

In a 1948 paper, then University of California scientist Edward C Tolman had hypothesised that rats have an internal map of their environment. However, until the new study, researchers were not able to show that a rat could actually control that map, using it to think about a place that happens to be different from where the rat is at that particular moment.

“This is a very important step,” said professor of neuroscience at New York University Langone Medical Center Gyorgy Buzsaki who was not involved in the study. “The hippocampus has the reputation of being the GPS of the brain. Many of us would like to know how (what happens there) is translated into footsteps.”

Although it makes sense that the initial signal to imagine a place would come from the hippocampus, Buzsaki said, it is “super, super difficult” to determine whether any action originates in one part of the brain as opposed to another. The authors of the Science paper focused on place cells, which are found in the hippocampus. Grid cells, the other important part of the GPS system, live in a deep brain area called the entorhinal cortex, which is located close to the hippocampus.

The experiments detailed in the Science paper required that scientists build from scratch machinery capable of reading and then translating the rat’s internal map, to determine what the rodent is thinking at one particular moment.

Lai began work on the project nine years ago after arriving at the Institute’s Janelia Research Campus in Ashburn, Virginia. He told two of his eventual co-authors on the paper – his adviser senior fellow Timothy Harris and Howard Hughes Medical Institute investigator Albert Lee – that he had ideas that would allow them to test whether an animal can think.

Lai said it took four to five years just to build a real-time rat “thought detector”.

Researchers then had to design experiments that took into account what tasks a rodent would be able to perform. At the start, each rat had tiny electrodes implanted at 128 precise locations in its brain. The electrodes were then linked to a machine that would read the rat’s brain activity and learn the specific patterns generated as the rodent moved from one location to another. At each location, the rat’s brain produced a unique pattern of different cells firing at varying levels of intensity.

The rat was suspended with its feet touching a ball-shaped treadmill, which allowed it to navigate through the virtual reality arena. As the rat moved, the electrodes recorded its brain activity.

The scientists had to train the rats to run towards a visual cue in a two-dimensional virtual arena: a bouncing tower-like object. When the rodents touched the cue, they received a reward of sweetened water.

The machine also had to be trained. The machine learned to read the rat’s brain activity and translate it into specific locations in the virtual arena.

For the “teleporting” tests, scientists then disconnected the treadmill from the virtual reality arena. Now the rat could not use its feet to move itself in the arena. Instead, the rat had to imagine a remote location to reach that destination and receive the reward.

In the second test, the rat once again had to imagine a specific remote location, this time to move a virtual object to that position. Throughout the test, the rat remained in a fixed position in the arena.

“The amazing thing is that they learn it rather quickly,” said Lee, who now works at Beth Israel Deaconess Medical Center. He said the rats’ rapid learning suggests that it’s relatively natural for an animal to think about a place that is different from its actual location.

While three of the four rats tested were able to perform the experiments, a fourth was not. Lee said there are many possible explanations for the failure of the fourth. For example, the rat could have sustained some slight damage to the hippocampus.

“This is a moderately complex (task), and it could be the case that not every animal can do it,” he said. “The fact that three out of four animals were doing it well, that suggests it is a very solid ability of rats to imagine remote locations.” – Mark Johnson

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