(CN) – Researchers on Thursday reported the first evidence that animals can mentally replay past events from memory – a discovery that could aid the development of new drugs to treat Alzheimer’s disease.
The team’s findings were published in the journal Current Biology.
“The reason we’re interested in animal memory isn’t only to understand animals, but rather to develop new models of memory that match up with the types of memory impaired in human diseases such as Alzheimer’s disease,” said lead author Jonathon Crystal, a professor in the Indiana University Bloomington College of Arts and Sciences’ Department of Psychological and Brain Sciences.
Crystal said most preclinical studies on potential new Alzheimer’s drugs analyze how these compounds affect spatial memory, one of the easiest forms of memory to evaluate in animals. However, the loss of spatial memory is not what causes the most debilitating effects of Alzheimer’s.
“If your grandmother is suffering from Alzheimer’s, one of the most heartbreaking aspects of the disease is that she can’t remember what you told her about what’s happening in your life the last time you saw her,” said first author Danielle Panoz-Brown, an Indiana University doctoral student. “We’re interested in episodic memory – and episodic memory replay – because it declines in Alzheimer’s disease, and in aging in general.”
Episodic memory is the ability to recall past events. For example, if a person loses her car keys, she may try to recall every step – or “episode” – she took after leaving her vehicle. The ability to replay these episodes in order is known as episodic memory replay. Without this ability, people would not be able to make sense of most scenarios, Crystal said.
To assess animals’ episodic memory, the team spent nearly a year working with 13 rats they trained to memorize a list of up to 12 different odors. The rats were placed inside an enclosed platform featuring various odors and rewarded when they identified the fourth-to-last or second-to-last odor in the list.
The researchers changed the number of odors in the list before each test to verify the odors were identified based upon their position in the list, not by scent alone, confirming the rats were using their ability to recall the entire list in order. Platforms with different patterns were used to inform the rats as to which of the two options was sought.
Crystal said that, following their training, the rats successfully completed their tasks roughly 87 percent of the time overall – strong evidence that they were using episodic memory replay.
Additional experiments proved the rats’ recollections were long-lasting and resistant to “interference” from other memories, both signs of episodic memory. The team also conducted tests that temporarily suppressed activity in the hippocampus – the site of episodic memory – to verify the rats were using this part of their brain to complete their tasks.
Crystal said finding reliable methods for testing episodic memory replay in rats is urgent as new genetic tools are allowing researchers to create rats with neurological conditions similar to Alzheimer’s. Previously, only mice were available with the necessary genetic modifications.
“We’re really trying to push the boundaries of animal models of memory to something that’s increasingly similar to how these memories work in people,” Crystal said. “If we want to eliminate Alzheimer’s disease, we really need to make sure we’re trying to protect the right type of memory.”
The research was funded by the National Institutes of Health and the National Science Foundation.