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 identified a mechanism in the brain responsible for a common type of age-related memory loss.
The book, published today in Current biologysheds light on aging brain function and may deepen our understanding of Alzheimer’s disease and similar disorders in humans.
“We’re trying to understand normal memory and why a part of the brain called the hippocampus is so essential for normal memory,” said lead author James Knierim, a professor at the university’s Zanvyl Krieger Mind/Brain Institute. “But also with many memory disorders, something is wrong in this area.”
Neuroscientists know that neurons in the hippocampus, located deep in the temporal lobe of the brain, are responsible for a complementary pair of memory functions called pattern separation and pattern completion. These functions occur in a gradient through a tiny region of the hippocampus called CA3.
When these functions are out of balance, memory is impaired, causing symptoms such as forgetfulness or repetition. The Johns Hopkins team found that as the brain ages, this imbalance may be caused by the disappearance of the CA3 gradient; the pattern separation function fades out and the pattern completion function takes over.
Neurons responsible for pattern separation are generally more prevalent in the region proximal to the CA3 area, while those responsible for pattern completion are prevalent in the distal region, said lead author Heekyung Lee, associate 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 dominance in pattern completion.
In normal brains, pattern separation and pattern completion work hand in hand to sort and make sense of perceptions and experiences, from the most basic to the most complex.
If you visit a restaurant with your family and a month later you visit the same restaurant with friends, you should be able to recognize that it was the same restaurant, even if some details have changed – c is the completion of the model.
But you also need to remember which conversation happened when, so that you don’t confuse the two experiences – this is the separation of models.
When pattern separation disappears, pattern completion dominates the process. With your brain focused on the common restaurant experience to the exclusion of the details of separate visits, you might remember a conversation about traveling to Italy during a visit, but you’re wrong who was talking.
“We all make these mistakes, but they tend to get worse as we get older,” Knierim said.
In experiments, researchers compared young rats with intact memory to older rats with intact memory and older rats with impaired memory.
As older rats with intact memory performed water maze tasks as well as younger rats, neurons in the CA3 regions of their hippocampus were already beginning to favor pattern completion at the expense of pattern separation.
Since this physiological discovery had not manifested in their behavior, the researchers concluded that something was causing the rats to compensate for the deficit.
This finding resonates with humans who remain surprisingly lively into their old age, the researchers say. Thus, identifying the mechanism of memory loss could lay the groundwork for learning what prevents memory impairment in some humans, and therefore how to prevent or delay cognitive decline in the elderly.
“If we can better understand what these compensatory mechanisms are, then we may be able to help prevent cognitive decline with aging,” Knierim said. “Or, if we can’t stop it, maybe we can enhance other parts of the brain to compensate for the losses that occur.”
The other lead authors on the paper were Michela Gallagher, Krieger-Eisenhower Professor of Psychology and Neuroscience at Johns Hopkins, and Scott Zeger, Professor of Biostatistics at the Johns Hopkins Bloomberg School of Public Health. Gallagher’s lab previously demonstrated that the anti-epileptic 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 these drugs to deficits in the future.
“It would give us more control over where we could possibly target the deficits we see,” she said.
About this aging and memory research news
Author: Press office
Source: Johns Hopkins University
Contact: Press Office – Johns Hopkins University
Picture: Image is in public domain
Original research: Access closed.
“Loss of functional heterogeneity along the CA3 transverse axis during aging” by Heekyung Lee et al. Current biology
Loss of functional heterogeneity along the CA3 transverse axis during aging
- Young rats (Y) 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 distinct environments
- Aged rats without memory impairment show intermediate trends between Y and AI rats
Age-related deficits in pattern separation have been postulated to bias hippocampal memory processing output toward pattern completion, which may lead to deficits in accurate memory retrieval.
Although the CA3 region of the hippocampus is often conceptualized as a seamless network involved in pattern completion, growing evidence demonstrates a functional gradient in CA3 along the transverse axis, as outputs separated by a model (dominant in the more proximal CA3) pass to a completed model. outlets (dominant in the more distal CA3).
We examined neural representations along the CA3 transverse axis in young (Y), aged without memory impairment (AU) and aged with memory impairment (AI) rats when different changes were made to the environment.
Functional heterogeneity in CA3 was observed in Y and AU rats when environmental similarity was high (altered signs or altered environmental shapes in the same room), with more orthogonalized representations in proximal CA3 than in distal CA3.
In contrast, IA rats showed reduced orthogonalization in the proximal CA3 but showed normal (i.e., generalized) representations in the distal CA3, with little evidence of a functional gradient.
Under experimental conditions where environmental similarity was low (different rooms), representations in the proximal and distal CA3 were remapped in all rats, showing that the CA3 of AI rats is able to encode distinctive representations for inputs with a greater dissimilarity.
These experiments support the hypotheses that the age-related bias towards hippocampal template completion is due to the loss in IA rats of the normal transition from template separation to template completion along the transverse axis CA3.
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