Researchers uncover why mental maps fade with age

The findings seem to align with human behavior. “Older people often can navigate familiar spaces, like their home or the neighborhood they’ve always lived in, but it’s really hard for them to learn to navigate a new place, even with experience,” Giocomo said.

In contrast, both young and middle-aged mice understood the assignment by day six, and their grid cell activity swiftly matched whichever track they were on.

“Over days one through six, they have progressively more stable spatial firing patterns that are specific to context A and specific to context B,” Herber said. “The aged mice fail to the develop these discrete spatial maps.”

The middle-aged mice had somewhat weaker patterns in their brain activity, but they performed very similarly to the young mice. “We think this is a cognitive capacity that at least until about 13 months old in a mouse, or maybe 50 to 60 years old in a human counterpart, is probably intact,” Herber said.

Super-ager

Though young and middle-aged mice performed uniformly within their age groups, the oldest set showed more variability in spatial memory.

Male mice generally performed better than female mice, though the researchers do not yet know why.

One elderly male mouse stood out: It aced the test, remembering the hidden reward locations on alternating tracks just as well as, if not better than, the young and middle-aged mice.

“It was the very last mouse I recorded and, honestly, when I was watching it run the experiment, I thought, ‘Oh no, this mouse is going to screw up the statistics,’” Herber said.

Instead, the super-ager mouse turned out to confirm the link between grid cell activity and spatial memory. Its grid cells were as unusually sprightly as its behavior, firing clearly and accurately in each environment.

“The variability in the aged group allowed us to establish these correlative relationships between neural function and behavior,” Herber said.

The super-ager mouse also encouraged the researchers to look for genetic differences that might underly variability in aging. They sequenced the RNA of young and old mice and found 61 genes that were more expressed in mice with unstable grid cell activity. These genes could be involved in either driving or compensating for spatial memory decline, the researchers said.

The gene Haplin4, for example, contributes to the network of proteins that surround neurons, known as the perineuronal net, which could help shore up grid cell stability and protect spatial memory in aging mice.

“Just like mice, people also exhibit a variable extent of aging,” Herber said. “Understanding some of that variability — why some people are more resilient to aging and others are more vulnerable — is part of the goal of this work.”

Researchers at the University of California, San Francisco, contributed to the study.

The study received funding from the Simons Foundation, the Stanford University Medical Scientist Training Program, the National Institute on Aging, the National Institutes of Health BRAIN Initiative (grant U19NS118284), National Institute of Mental Health (grants MH126904 and MH130452), the National Institute on Drug Abuse (grant DA042012), the Vallee Foundation and the James S. McDonnell Foundation.