Scientists find brain region responsible for memory decline with aging

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New research on rats could help scientists find treatments for age-related memory loss. Camille Chambefort/EyeEm/Getty Images
  • The researchers studied the neural mechanisms behind cognitive decline in rats.
  • Their research suggests that some older adults may be resilient to cognitive decline, despite age-related effects at the neural level.
  • The researchers concluded that further research into these compensatory mechanisms could help develop treatments for age-related cognitive decline.

Research suggests that the hippocampus, an area of ​​the brain responsible for memory, performs two complementary processes: pattern separation and pattern completion.

Model completion can be described as the ability to remember having visited a place when you return to it a month later, even if some details have changed. On the other hand, model separation is about remembering the conversations that happened during each visit and not confusing them with each other.

As humans and rodents age, their pattern separation abilities decline. Studies have shown that this may be related to an overactive CA3 network in the dentate gyrus of the hippocampus. Drugs that reduce this hyperactivity increased memory performance in aged rats.

A direct study of the effect of the CA3 network on memory could help researchers develop treatments to improve age-related memory problems. More recently, researchers investigated how this CA3 network influenced the memory abilities of young and old rats.

The researchers found that some aged rats could perform memory tasks similar to those of young rats, even though their brains had deficits in pattern separation.

The study was published inCurrent biology.

For the study, the researchers got four young rats (between 3 and 6 months old) and 14 older rats (between 22 and 26 months old). To begin with, the rats underwent behavioral tests in a water maze.

They then underwent hyperdrive implantation surgery so the researchers could monitor the lateral edge of their CA3 brain region.

Afterwards, they were trained for eight days to locate an escape platform submerged in a water maze tank. Every sixth time in the maze was considered a “probe trial” and did not include any escape platforms for the first 30 seconds.

The researchers used the average search proximity scores of the rats during these probe trials to calculate a learning index. Mice with a score greater than 240 were categorized as “impaired aged memory”, while those with a learning index below 240 were “unimpaired aged memory”.

The researchers then further analyzed the cognitive abilities of the rats during foraging sessions, circular track training and other water maze tests.

As expected, they found that older rats with memory impairment performed worse on various tasks than younger rats and this was consistent with hyperactivity in parts of the CA3 area of ​​the brain. hippocampus.

They also found, however, that some of the older rats without memory impairment behaved similarly to the younger rats, even though they showed signs of the same changes in their CA3 regions.

To explain the findings, the researchers noted that in neurological conditions such as Alzheimer’s disease and Parkinson’s disease, there is little behavioral deficit until a threshold is crossed.

They said this may explain why some older rats performed similarly to younger rats, given that their maze scores occurred on a continuum between the scores of the younger rats and those of the more impaired older rats. .

Asked about the underlying mechanisms, Heekyung Lee, of Johns Hopkins University’s Knierim Laboratory and lead author of the study, said Medical News Today that inhibitory neurons may play a role.

“The number of inhibitory neurons decreases with age in the hippocampus. priority work […] showed that while inhibitory neurons in several subregions of the hippocampus decrease in both aged rats without memory impairment (AU) and with memory impairment (AI), inhibitory neurons specifically in the hilum from the dentate gyrus subregion decrease in AI, but not in AU rats,” Lee explained.

“It should be noted that there are complex feedforward and feedback connections between the dentate gyrus and the proximal CA3, two subregions that support pattern separation calculations. The balance between excitation and inhibition plays a critical role in network dynamics,” she added.

“A possible compensation mechanism in [aged] rats [with unimpaired memory] may be that the preservation of inhibitory neurons exclusively in the [brain’s] The hilum region may be sufficient to overcome age-related excitation-inhibition imbalance to promote pattern separation.
— Heekyung Lee, study author

Dr. Tara Swart Bieber, neuroscientist and professor at MIT Sloan School of Management, said DTM that neuroplasticity could also play a role.

“Neuroplasticity – the ability to rewire our brains throughout life – is likely the mechanism underlying this compensation. Although more difficult later in life, it is possible to make new connections that can circumvent pathways that have become weak. […] Also, people can fully recover after a stroke or brain surgery,” she said.

The researchers concluded that further research is warranted to understand compensatory mechanisms in aged rats without memory impairment to understand how they prevent age-related cognitive decline.

Asked about future research directions, Lee said determining different neuron subtypes would be key for targeted therapies.

“Future research to understand why inhibitory neurons are vulnerable to aging may help uncover therapeutic strategies to increase inhibition in the hippocampus to help improve age-related memory problems.”
— Heekyung Lee, study author

“Furthermore, there are different subtypes of inhibitory neurons, and understanding the functional specificity of each subtype may allow targeted intervention,” she added.

Dr. Bieber also said that research into lifestyle habits that may help older people manage their age more effectively could also improve understanding of these compensatory mechanisms.

Asked more generally about preventing age-related memory decline, Dr Bieber said:

“Engaging in new learning throughout your life, i.e. attention intense enough to change your brain, for example, learning a new language, sport, musical instrument, etc. is the best thing you can do for your brain as an adult.”


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