Cell: Mechanisms associated with age-related memory loss in rodents

Research in mice by neuroscientists at Johns Hopkins University has identified a mechanism in the brain responsible for a common age-related memory lo.

"We're trying to understand normal memory and why a part of the brain called the hippocampus is so important for normal memory," said senior author James Knirim

Ageing increases our susceptibility to memory disturbances, and computational studies have shown that to reduce this disturbance, neurons in the hippocampus, located deep in the brain's temporal lobe, undertake two complementary process.

In the normal brain, pattern separation and pattern completion work together to categorize and understand perception and experience, from the most basic to the highly compl.

These functions are thought to occur in gradients in a small region called CA3 in the hippocamp.

The authors set out to investigate "how an imbalance in the normal gradient of pattern separation and pattern completion along the transverse axis of CA3 contributes to age-related dysfuncti.

Lead author .

Heekyung Lee said neurons responsible for pattern separation were generally more prevalent in proximal regions of the CA3 area, while neurons responsible for pattern completion were prevalent in distal regio.

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Heekyung Lee is an Assistant Research Scientist at the Mind/Brain Institu.

With age, neural activity in proximal regions becomes hyperactive, and the interaction between these two regions becomes abnormal, creating an advantage in pattern completi.

So, when modal separation disappears, modal completion will overwhelm the proce.

When your brain focuses on the shared experience at a restaurant and ignores the details of a separate visit, you might remember a conversation about a trip to Italy during a visit, but miss who was speaki.

"We all make these mistakes, but they tend to get worse as we age," Knelim sa.

In their experiments, the researchers compared multiple tasks in young (Y) rats with unimpaired memory, old (AU) rats with unimpaired memory, and old (AI) rats with impaired memory performan.

They noted that the findings "support the hypothesis that the age-related bias in hippocampal pattern completion is due to the loss of the normal transition from pattern separation to pattern completion in the CA3 transverse axis in AI ra.

"

The results also showed that when memory-unimpaired old rats performed the water maze task as young rats, neurons in the CA3 region of the hippocampus had begun to support pattern completion at the expense of abandoning pattern dissociati.

Because this physiological finding wasn't reflected in their behavior, the researchers concluded that there was something that allowed the mice to make up for the defic.

The findings have also been confirmed in humans, who remain surprisingly sharp into old age, the researchers sa.

"Although memory function is susceptible to aging, a subset of aged animals, including older humans, are able to maintain normal memory function," they wro.

"Although the Union mice did not show a statistical difference between the AI ​​mice in the current study, they also did not show a statistical difference from the Y mice, suggesting that the AU mice were not like the AI-impaired mi.

it appears that the AU mice may be physically impaired in behavior, but have not yet crossed a thresho.

" The team believes that in the aging process , it is also possible that there are adaptive compensatory mechanisms at work that allow animals to perform well when brain changes cause dysfuncti.

Therefore, pinpointing the mechanisms of memory loss could lay the groundwork for understanding what prevents memory impairment in some people, and thus how to prevent or delay cognitive decline in older adul.

"If we can better understand what these compensatory mechanisms are, then maybe we can help prevent cognitive decline with age," Knelim sa.

"Or, if we can't stop it, maybe we can enhance other parts of the brain to compensate for the damage that's happeni.

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The paper's other senior authors are Mikaela Gallagher, ., the Krieger-Eisenhower Professor of Psychology and Neuroscience at Johns Hopkins University, and Scott Zeger, ., John Hope Professor of Biostatistics at Kings University Bloomberg School of Public Heal.

Gallagher's lab previously demonstrated that the antiepileptic drug levetiracetam improves memory performance by reducing hyperactivity in the hippocamp.

"The anti-seizure drug levetiracetam to reduce ADHD improves mild cognitive impairment in aged rats and amnesia," the researchers wrote in their paper in the journal Current Biolo.

memory performance in patients, suggesting that normalizing CA3 ADHD restores the balance between pattern dissociation and pattern completi.

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Li also speculates that new, more specific information about how memory impairment occurs may allow scientists to better target these deficits with drugs in the futu.

"This will give us better control over the deficit targets we may see," she sa.

Original title:

Loss of functional heterogeneity along the CA3 transverse axis in aging