How these mice navigating a virtual reality game can help Alzheimer’s patients

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New York researchers have developed a virtual reality mouse maze in an effort to demystify a question that has plagued neuroscientists for decades: How are long-term memories stored?

What they found surprised them. After forming in the hippocampus, a curved structure that sits deep in the brain, the mice’s memories were actually rooted in what’s called the anterior thalamus, an area of ​​the brain that scientists don’t typically associate not at all to memory processing.

“The fact that the thalamus is the clear winner here was very interesting to us and unexpected,” said Priya Rajasethupathy, an associate professor at Rockefeller University and one of the co-authors of a peer-reviewed study published in the journal Cell. this week. The thalamus “has often been thought of as a sensory relay, not very cognitive, not very important in memory”.

This new research, however, indicates that it could play a vital role in converting short-term memories into long-term ones. And Rajasethupathy said this should make the thalamus a key area of ​​study for researchers trying to help patients with conditions such as Alzheimer’s disease, who are able to recall old memories but may have difficulty. trouble remembering new information.

“It involves a part of the brain – the thalamus – in the long-term storage of memories in a way that hasn’t even been assumed by anyone else,” said Loren Frank, professor of physiology at the University. ‘University of California, San Francisco, which was not involved in the study.

Rajasethupathy noted that neuroscientists have long known that memories take shape in the hippocampus and are the focus of the vast majority of research into conditions such as amnesia and Alzheimer’s disease.

Previous research has “lead to this pattern where memories form in the hippocampus but then become independent over time and slowly stabilize in the cortex,” the outermost wrinkled part of the brain. The question has been exactly how memories travel from region to region, Rajasethupathy said.

“This process has been mysterious, I would say, for over 50 years,” Rajasethupathy said.

It was a good time for her lab to try to find an answer, she added, thanks to new technology that allowed researchers to track activity in multiple parts of each subject’s brain. The innovations allowed the team to trace how memories travel when mice learned to navigate a maze.

“I think what they did was technically very difficult,” Frank said. “Especially when they were trying (to observe) the activity of multiple neurons in three different areas at once, using these type of fiber microscopes. It’s a state-of-the-art thing.

The study – led by Rockefeller graduate students Andrew Toader and Josue Regalado, working in Rajasethupathy’s lab – involved strapping the mice into a helmet designed to keep them stable while a machine used fiber optics to record their activity cerebral.

The maze took them to various “rooms” that offered either incentives, like sugar water, or deterrents, like a puff of air to the face.

The mice returned to the maze for days, enough time to create long-term memories.

“The analogy would be your birthday dinner versus the dinner you had three Tuesdays ago,” Toader said in a statement. “You’re more likely to remember what you ate on your birthday because it’s more rewarding for you — all your friends are there, it’s exciting — compared to a typical dinner party, which you remember. maybe remember the next day but probably not a month later.”

Meanwhile, the researchers used chemicals to inhibit parts of the mice’s brains to determine how this affected their ability to create and store memories.

Not only did they find that the anterior thalamus was a crucial landmark for these memories, but they also discovered that by stimulating this area of ​​the rodent brain, the researchers were “able to help mice retain memories that ‘they would usually forget,’ according to a press release about the study.

Rajasethupathy added, “Some memories are more important to us than others. We found that not only do mice need the anterior thalamus to consolidate their memories, but by activating it, we could improve the consolidation of a memory that mice usually forget.

Rajasethupathy noted that there were some limitations to the study. This does not indicate, for example, that traveling through the anterior thalamus is the only route memories can take for long-term storage.

“I want to be clear that this is not the end, everything will be everything,” she said. “Perhaps not everything is consolidated this way. But I am very confident that it is a very important circuit.

This study also relied on mice, which do not have the same brain as humans, but which have proven to be extremely useful models for discovering how our own brain works. The long-term memory storage process takes weeks in rodents, whereas it can take months in humans, Rajasethupathy added.

It’s also possible that different types of memory take different highways, she noted. There are explicit memories, which focus on specific facts, figures, and data points, and implicit memories are usually tied to emotion and can form without a person realizing it. The thalamus may not intervene in the same way for the two types of information.

But Frank, a UCSF professor, said the study will have broad implications for future research, spurring more investigations into the role of the thalamus in memory storage.

“It’s good for the field to get to the point where we can think about the long-term evolution of memories and really try to figure out how it works,” he said. “And the study is definitely a step in that direction.”


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