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


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Researchers in New York developed a virtual reality maze for mice in an attempt to demystify a question that’s been plaguing neuroscientists for decades: How are long-term memories stored?

What they found surprised them. After forming in the hippocampus, a curved structure that lies deep within the brain, the mice’s memories were actually rooted through what’s called the anterior thalamus, an area of the brain that scientists haven’t typically associated with memory processing at all.

“The thalamus being a clear winner here was very interesting for us, and unexpected,” said Priya Rajasethupathy, an associate professor at Rockefeller University and one of the coauthors 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 to long-term memories. And Rajasethupathy said that should make the thalamus a key area of study for researchers attempting to help patients who suffer from conditions such as Alzheimer’s, who are able to recall old memories but may have trouble remembering new information.

“it implicates a part of the brain — the thalamus — in the long-term storage of memories in a way that wasn’t even hypothesized by anyone else,” said Loren Frank, a professor of physiology at the University of California San Francisco, who was not involved in the study.

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

Past research has “led to this model where memories are formed in the hippocampus but then become independent over time and slowly stabilized in the cortex,” the wrinkled, outermost portion of the brain. The question has been exactly how memories travel from one area to another, Rajasethupathy said.

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

It was the right time for her lab to attempt to pinpoint 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 enabled the team to trace how memories are traveling as the mice learned to navigate a maze.

“I think what they did was technically very challenging,” Frank said. “Particularly where they were trying to (observe) activity from multiple neurons in three different areas at once, using this sort of fiber microscopes. That’s a pretty state of the art thing.”

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

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

The mice returned to the maze for days, enough time for them 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 had on your birthday because it’s more rewarding for you—all your friends are there, it’s exciting—versus just a typical dinner, which you might 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 it 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 that area in the rodents’ brains, the researchers were “able to help mice retain memories that they would usually forget,” according to a news 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 that by activating it, we could enhance consolidation of a memory that mice would usually forget.”

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

“I want to be clear that this is not the end all be all,” she said. “Maybe everything isn’t consolidated through this pathway. But I’m very confident this is one very important circuit.”

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

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

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

“It’s nice for the field to getting 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.”


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