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Brain Mechanism Linked to Age-Related Memory Loss Discovered – Neuroscience News

Summary: Researchers have identified a mechanism that occurs in the CA3 region of the hippocampus that appears to be responsible for a common type of age-related memory loss.

Source: Johns Hopkins University

Working with rats, neuroscientists at Johns Hopkins University have discovered a mechanism in the brain responsible for a common type of age-related memory loss.

The work, published today in current biologysheds light on how the aging brain works and may deepen our understanding of Alzheimer’s disease and similar conditions in humans.

“We’re trying to understand normal memory and why a part of the brain called the hippocampus is so crucial to normal memory,” said senior author James Knierim, a professor at the university’s Zanvyl Krieger Mind/Brain Institute. . “But something goes wrong in this area even with many memory disorders.”

Neuroscientists know that neurons in the hippocampus, deep in the brain’s temporal lobe, are responsible for a complementary pair of memory functions called pattern separation and pattern completion. These functions take place in a gradient over a small region of the hippocampus called CA3.

When those functions become unbalanced, memory is impaired, causing symptoms such as forgetfulness or repetition. The Johns Hopkins team found that as the brain ages, this imbalance can be caused by the CA3 gradient disappearing; the cartridge separation function disappears and the cartridge completion function takes over.

Neurons responsible for pattern separation tend to be more common in the proximal region of the CA3 region, while those responsible for pattern completion occur in the distal region, said lead author Heekyung Lee, an assistant researcher at the Mind/Brain Institute, with aging, neural activity in the proximal region becomes overactive and the interaction between the two regions becomes abnormal, creating a dominance in pattern completion.

In normal brains, pattern separation and pattern completion work hand in hand to organize and understand perceptions and experiences, from the most basic to the very complex.

If you visit a restaurant with your family and visit the same restaurant with friends a month later, you should be able to recognize that it was the same restaurant, even if some details have changed – this is the completion of the pattern.

But you also need to remember which conversation happened when so you don’t confuse the two experiences – this is pattern separation.

When pattern separation disappears, pattern completion dominates the process. With your brain focused on the communal experience of the restaurant, to the exclusion of the details of the individual visits, you may remember a conversation about a trip to Italy during one visit, but be mistaken who was speaking.

“We all make these mistakes, but they only get worse as we get older,” Knierim said.

In experiments, the researchers compared young rats with unaffected memory with older rats with unimpaired memory and older rats with poor memory.

While the older rats with unimpaired memory performed maze tasks in the water just as well as young rats, the neurons in the CA3 regions of their hippocampi were already beginning to favor pattern completion at the expense of pattern separation.

That finding is repeated in people who remain surprisingly sharp in their older years, the researchers say. Image is in the public domain

Because that physiological finding was not reflected in their behavior, the researchers concluded that something enabled the rats to make up for the deficiency.

That finding is repeated in people who remain surprisingly sharp in their older years, the researchers say. So pinpointing the amnesia mechanism could lay the groundwork for learning what prevents amnesia in some people, and thus how to prevent or slow cognitive decline in the elderly.

“If we can better understand what these compensatory mechanisms are, we may be able to help prevent cognitive decline with aging,” Knierim said. “Or, if we can’t stop it, maybe we can improve other parts of the brain to make up for the losses that occur.”

Other senior authors of the paper were Michela Gallagher, Krieger-Eisenhower professor of psychology and neuroscience at Johns Hopkins, and Scott Zeger, professor of biostatistics at Johns Hopkins’ Bloomberg School of Public Health. Gallagher’s lab previously showed that the anti-seizure drug Levetiracetam improves memory performance by reducing hyperactivity in the hippocampus. So Lee also speculates that this new, more specific information about how memory impairments occur could allow scientists to better target such drugs at the deficits in the future.

“It would give us better control over where we could target the deficits we see,” she said.

About this news about aging and memory research

Writer: press office
Source: Johns Hopkins University
Contact: Press Office – Johns Hopkins University
Image: The image is in the public domain

Original research: Closed access.
Loss of functional heterogeneity along the CA3 transverse axis in agingby Heekyung Lee et al. current biology


Also see

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Loss of functional heterogeneity along the CA3 transverse axis in aging


  • Young (Y) rats show transition from pattern separation to pattern completion in CA3
  • Aged rats with memory impairment (AI) show pattern completion in proximal and distal CA3
  • AI rats can orthogonalize representations in two spatially different environments
  • Aged rats with amnesia show trends intermediate between Y and AI rats


It has been postulated that age-related deficiencies in pattern separation bias the output of hippocampal memory processing toward pattern completion, which may cause deficiencies in accurate memory retrieval.

Although the CA3 region of the hippocampus is often conceptualized as a homogeneous network involved in pattern completion, growing evidence shows a functional gradient in CA3 along the transverse axis, as pattern-separated outputs (dominant in the more proximal CA3) transition to pattern-completed exits (dominant in the more distal CA3).

We examined the neural representations along the CA3 transverse axis in young (Y), old memory-unaffected (AU), and aged memory-impaired (AI) rats when various environmental changes were made.

Functional heterogeneity in CA3 was observed in Y and AU rats when environmental similarity was high (altered signals or altered environmental shapes in the same chamber), with more orthogonal representations in proximal CA3 than in distal CA3.

In contrast, AI rats showed reduced orthogonalization in proximal CA3, but showed normal (i.e., generalized) representations in distal CA3, with little evidence of a functional gradient.

Under experimental conditions where environmental similarity was low (several chambers), representations in proximal and distal CA3 were reassigned in all rats, demonstrating that AI rat CA3 is able to encode discriminatory representations for inputs of greater dissimilarity.

These experiments support the hypotheses that the age-related propensity for hippocampal pattern completion is due to the loss in AI rats of the normal transition from pattern separation to pattern completion along the CA3 transverse axis.

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