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Researchers at University of Georgia report discovery of “episodic-like” memory in laboratory rats, possibly opening new avenues for research on Alzheimer’s disease


WEBWIRE

Jul 10, 2006, Athens, Ga. – Human memory is a mental scrapbook, filled with moments of luminous happiness or unforgettable sorrow. We remember the day we said “I do,” and the first glimpses of our children and grandchildren. But among the elderly, pages often go missing from the scrapbooks of their memory, and those with Alzheimer’s disease or amnesia may have nothing left of their memorable lives at all.

Researchers have long sought animal models to help them study memory and have repeatedly asked one question: Are humans the only ones who remember unique, personal past experiences, or can animals do it, too? Now, researchers from the University of Georgia are closer to solving the problem.

Psychologists from UGA report in the new issue of Current Biology that laboratory rats have a detailed representation of remembered events and therefore also likely have episodic-like memory. The finding gives researchers an animal model that could help in understanding how humans with Alzheimer’s or amnesia lose their memory.

“Understanding whether animals have this kind of memory has been a challenge for years,” said Jonathon Crystal, an associate professor of psychology who directed the research. His co-author on the paper was Stephanie Babb, a former Ph.D. student at UGA and now a post-doctoral fellow at the University of Texas Medical School in Houston. “What we have always needed is a model animal with which we can ask questions about the neural basis of episodic memory.”

The new findings could be a first step toward testing new drugs in rats for humans with diseases such as Alzheimer’s or amnesia.

Crystal and Babb used a radial maze, an eight-armed device with a central hub, in which laboratory rats were able to search for specific foods and relate their presence or absence to remembered cues. Each arm has a door at the junction with the central hub so the rats can choose which of the eight arms to go into.

“If rats have specific information about the content of events they experienced in the past, together with the knowledge of when and where those events occurred, then they should adjust their behavior to the temporal and spatial constraints of food availability,” said Crystal. “To address this question, we trained rats to discriminate what, where and when they encountered food.”

To do this, they provided rats with access to locations baited with distinctive flavors such as grape or raspberry and non-distinctive flavors such as the chow the animals are usually fed. The researchers then replenished the food locations with distinctive flavors after a long but not a short delay and didn’t replenish the locations with non-distinctive flavors at all.

They further complicated the rats’ choices by either pre-feeding them with the distinctive flavor so they would be full or by pairing it with nauseating lithium chloride. This “devalued” selected distinctive flavors. To the researchers’ surprise, the rats then selectively decreased their return visits to the “devalued distinctive flavor” while continuing to return regularly to the flavors that hadn’t been so devalued.

By replicating the tests, the psychologists were able to show conclusively that the rats possessed “episodic-like memory,” something that had never been proved in any laboratory mammal, though such behavior has been demonstrated in scrub jays.

Earlier research by Crystal and numerous other researchers has shown that rats don’t navigate well by smell, and the UGA experiments were designed to rule out other reasons why the rats returned to food sources in the radial maze at certain times.

“The most surprising thing to us was that the rats solved the problem,” said Crystal. “People have been trying to document episodic-like memory in rats for a while, and they haven’t succeeded. This is basic science that has the potential to translate into the clinical realm.” (Other scientists have also long attempted to prove such memory in monkeys and have not yet succeeded in showing that, either.)

The research was supported by grants from the National Institute of Mental Health.



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