Animal Memory Discovery Could Lead to New Alzheimer's Treatments

Scientists have uncovered the first evidence that animals can mentally replay past events from memory—a discovery that could help develop new treatments for Alzheimer's disease.

For a new study, published in the journal Current Biology, researchers from Indiana University (IU) wanted to investigate animal memory in order to develop new models that will help our understanding of memory impairment in human neurological disorders.

Currently, most preclinical studies on potential new Alzheimer's drugs look at how a given compound affects spatial memory—one of the easiest types to assess in animals—lead author of the study Jonathon Crystal, a neuroscientist at IU, said in a statement.

However, the most debilitating effects of Alzheimer's aren't usually caused by damage to spatial memory. Instead, it is the loss of so-called episodic memory that has the most impact.

Episodic memory is the ability to remember specific events in sequential order, which allows us to recall past experiences moment-by-moment by "replaying" them in our minds (an ability known as episodic memory replay). This enables us to make sense of our experiences, something that Alzheimer's patients struggle with because they can't remember the order in which things occur.

"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," Danielle Panoz-Brown, an IU Ph.D. student and the first author of the study, said in the statement. "We're interested in episodic memory—and episodic memory replay—because it declines in Alzheimer's disease, and in aging in general."

Over the course of a year, the Indiana researchers assessed the ability of 13 rats to replay past events from memory. They did this by training them to memorize lists of up to 12 different odors in order, using rewards. The odors came from scented plastic lids, which were placed in holes in the floor of specially made enclosures. When the rats identified the right lid, in the right order, they were given food.

After their training, the team assessed the rats' memory of the odor lists by placing them in enclosures, with patterns of scented plastic lids in the floor that varied slightly with each test. In these assessments, the rats were given rewards when they identified the second-to-last or fourth-to-last odor on the list.

To ensure that the animals were recalling the whole list in order and not simply relying on the scent of familiar smells, the researchers changed the number of odors on the list before each test.

The results showed that the rodents completed their tasks successfully around 87 percent of the time across all the trials—strong evidence that they were employing episodic memory replay, according to the scientists.

Furthermore, the team conducted additional tests that demonstrated these memories were long-lasting and resistant to "interference" from other memories, which are features of episodic memory. They also conducted experiments that suppressed the site of episodic memory in the brains of the rats—the hippocampus—to confirm that this region was being employed when they were tasked with remembering the odors.

Being able to reliably test episodic memory in these animals is important, according to Crystal, because new genetic techniques are enabling scientists to create rats with neurological conditions similar to Alzheimer's—something that until recently was only possible in mice.

"We're really trying push the boundaries of animal models of memory to something that's increasingly similar to how these memories work in people," he 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."