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Gray Matters: Brain's Sleep-Time Memory Storage Gets Muddled with Age

New study finds that the brain's memory filing system, which relies on repeating the events during sleep, gets out of whack in older rats


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A new study may help explain why people of a more advanced age forget where they put their keys, hid important documents—or even who was on hand during a recent outing.

University of Arizona in Tucson researchers report in The Journal of Neuroscience that forgetfulness may, at least in part, stem from a breakdown in the brain's ability to store or consolidate memories, a process that involves "replaying" and filing away events while we snooze.

In a study of rats, the scientists found that when the animals were at rest there were repeating patterns of neuronal (nerve cell) activity believed to be involved in moving information from short-term to long-term memory vaults in the brain. The process, however, was disrupted in the older rats.

The new work is the first to show that an animal's ability to store memories may be linked to the crispness of its recollections. Among the older rats, replay occurred, but their brains scrambled the sequences in which the neurons fired (transmitted electrical impulses to communicate with neighboring cells).

"Memory does change during the process of normal aging, and it happens in all of us," says study co-author Carol Barnes, a neuroscientist. "If you're playing an experience in the wrong order, it's not going to faithfully allow you to retrieve an accurate memory in the end."

Boston University neuroscientist Michael Hasselmo, who was not involved in the study, says the findings provide compelling evidence that at least some age-related memory loss may be due to faulty storage and may pave the way for new drugs designed to enhance memory replay.

Barnes and her team compared memory consolidation and performance in 11 young male rats (aged 11 to 12 months) and 11 older males (25 to 31 months old). (She says this would be similar to comparing 35-year-old men to those in their seventies). The team implanted electrodes in each rat's hippocampus—a midbrain region responsible for short-term and episodic memory of places and people as well as emotions linked to specific events.

Neuroscientists have believed since the early 1970s that neurons in the hippocampus reactivate in the same patterns during sleep as they did while recording activities as they were being performed. Studies have indicated that this repeated replay copies that information into the neocortex, the outermost layer of the brain where long-term memory storage takes place.

Researchers in this case recorded the activity in the hippocampuses of all 22 rats while they repeatedly navigated tracks and mazes in search of food. The exact patterns seen in the young animals as they completed the exercises played back as they slept; the sequences were garbled, however, in the older animals.

The team next gave the rats a series of spatial memory and learning exercises, such as a swim test in which a platform was submerged in a pool and the animals had to swim to it and perch on it. The young rats were able to remember where the platform was located from their training sessions, but the senescent ones spent more time swimming around trying to locate it. The older rats whose nighttime activity patterns most resembled their waking sequences, however, performed better than their fellow seniors.

Barnes says that she and her team are actively investigating possible drugs that might correct deficits in memory replay. "If we're able to reverse it, even a little bit, we should have better sequence reactivation," she says, which, in turn, could reduce forgetfulness. She notes that such a memory booster would benefit older as well as younger people. "There's a range of memory performance even in younger people," she says. "So, it could have applications to maximize memory, in general."