How These Mice Navigating a Virtual Reality Game Can Help Alzheimer’s Patients

(CNN) Researchers in New York have developed a virtual reality maze for mice 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 lying deep in the brain, the mice’s memories actually became ingrained in something called the anterior thalamus, an area of ​​the brain that scientists have not typically associated with memory processing at all.

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

However, this new research indicates that it could play a crucial role in converting short-term memories into long-term memories. And Rajasethupathy said this should make the thalamus an important area of ​​study for researchers trying to help patients suffering from diseases like Alzheimer’s who are able to recall old memories but may have trouble remembering remember new information.

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

In the office

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

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Previous research has “led to this model where memories are formed in the hippocampus but then become independent over time and slowly stabilize in the cortex, the wrinkly, outermost part of the brain.” The question was precisely how memories travel from one area to another, Rajasethupathy said.

“I would say this process has been mysterious for more than 50 years,” Rajasethupathy said.

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

“I think what they did was technically very challenging,” said Frank. “Especially where they were trying to (observe) the activity of multiple neurons in three different areas at the same time with this type of fiber microscope. It’s pretty cutting edge stuff.”

The study — led by Rockefeller graduate students Andrew Toader and Josue Regalado, who worked in Rajasethupathy’s lab — involved strapping the mice into a headpiece designed to keep them stable while a machine used optical fibers to record their brain activity.

The maze led them into different “rooms” that offered either stimulus like sugar water or deterrent like a puff of air in the face.

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

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

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

Not only did they find that the anterior thalamus was a crucial waypoint for these memories, they also found that by stimulating this area in the rodents’ brains, the researchers “were able to help mice preserve memories that they would normally forget,” the researchers said in 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 memories, but by activating it we could enhance the consolidation of a memory that mice would normally forget.”

What that means

Rajasethupathy noted that the study had some limitations. It doesn’t mean, for example, that the journey through the anterior thalamus is the only route memories can take on their way to long-term storage.

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

This study also relied on mice, which don’t have identical brains to humans, but have proven to be extremely useful models for discovering how our own brains work. The long-term memory storage process takes weeks in rodents, while it can take months in humans, Rajasethupathy added.

It’s also possible that different types of memories take different highways, she noted. There are explicit memories that focus on facts, numbers, and specific data points, and implicit memories are typically tied to emotions and can form without a person realizing it. The thalamus may not be equally involved in both types of information.

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But Frank, the UCSF professor, said the study will have far-reaching implications for future research, spurring further investigation into the role of the thalamus in memory storage.

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