Researchers have pinpointed a specific region of the brain that may explain why older adults often feel less familiar with their surroundings as they age.
Experts from Stanford University analyzed over a dozen mice similar in age to humans, ranging from 20 to 90 years old.
As the mice ran through virtual reality simulations, their brains’ medial entorhinal cortex fired off distinct patterns of neurons called grid cells.
The medial entorhinal cortex, nicknamed the brain’s ‘global positioning system,’ controls communication between the brain’s memory center, the hippocampus, and the cognitive function center, the neocortex.
Grid cells help create mental ‘maps’ of a space, which enables mice and humans to familiarize themselves with an area.
The team discovered that when young mice explored a space, grid cells in the medial entorhinal cortex fired in clear, organized patterns. But in older mice, as routines changed, the cells fired chaotically, evidence that their spatial memory had begun to break down.
Spatial memory, or memory for locations or directions, becomes severely impaired with forms of dementia like Alzheimer’s disease, suggesting the medial entorhinal cortex degrades with the disease.
This could pave the way for new treatments that specifically target this structure.
Researchers at Stanford University have uncovered a brain structure that may degrade in conditions like Alzheimer’s disease (stock image)
Dr Lisa Giocomo, senior study author, professor of neurobiology at Stanford Medicine, said: ‘You can think of the medial entorhinal cortex as containing all the components you need to build a map of space.
‘Before this study, there was extremely limited work on what actually happens to this spatial mapping system during healthy aging.’
The study, published Friday in the journal Nature Communications, looked at 18 mice divided into three categories based on age: three months old, 13 months old and 22 months old.
These ages roughly translate to 20-year-old, 50-year-old and 75- to 90-year-old humans.
The researchers recorded the brain activity of slightly thirsty mice while they ran through virtual reality tracks with a hidden reward, which was a lick of water.
The tracks involved running on a stationary ball surrounded by screens displaying a virtual environment, which the team compared to a mouse-sized treadmill in a mouse-sized IMAX theater.
Over the course of six days, the mice ran through the tracks hundreds of times. By the end of the experiment, mice in all age groups learned where the reward was on a particular track and only stopped at reward locations to lick.
As they learned the path, grid cells in their medial entorhinal cortex fired off distinct signals for each track, as if the mice were building custom mental maps.
But when mice were switched between two tracks they had already learned, each of which had a different reward location, elderly mice had trouble figuring out which track they were on.
Dr Giocomo said: ‘In this case, the task was more similar to remembering where you parked your car in two different parking lots or where your favorite coffee shop is in two different cities.’
The medial entorhinal cortex is pictured above in red. Experts believe it may degrade with aging and conditions like Alzheimer’s disease (stock image)
This led the older mice to sprint through the rest of the track without stopping to search for rewards. Several even tried licking everywhere instead.
In the confused older mice, their grid cells fired erratically instead of in the distinct patterns they had adopted when they got used to the tracks.
Dr Charlotte Herber, lead study author and MD-PhD student at Stanford Medicine, said: ‘Their spatial recall and their rapid discrimination of these two environments was really impaired.’
Dr Giocomo likened this to older people with signs of cognitive decline or dementia.
She said: ‘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.’
However, younger and middle-aged mice were able to adapt to the changes, and their grid cell activity matched the track they were on within six days.
Herber said: ‘Over days one through six, they have progressively more stable spatial firing patterns that are specific to context A and specific to context B.
‘The aged mice fail to develop these discrete spatial maps.’
Middle-aged mice had slightly weaker brain activity patterns, the team found, but they generally performed similarly to young mice.
Herber said: ‘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.’
The researchers said that based on the findings, older mice showed more variability in spatial memory. Male mice also performed better at the tests than female mice, though the team is unsure why.
The findings suggest the medial entorhinal cortex may be responsible for helping mice maintain mental maps as they age and could be one of the earliest structures to degrade in conditions like Alzheimer’s disease.
The study was partially funded by the National Institutes of Health.
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