Stem Cell Development and Memory Formation

July 17, 2012 § Leave a comment

It has heretofore been a great mystery as to how the brain is able to both store new memories while also maintaining older ones. Researchers at the RIKEN-MIT Center for Neural Circuit Genetics will be publishing a study in the March 30th issue of Cell that links memory formation to the birth of new neurons.

A specific type of neuron in the brain, dentate gyrus, plays a discrete role in memory formation. This apparently depends on the age of the neural stem cells that produced them. An imbalance between old and new brain neurons can actually disrupt memory formation while an individual is aging or has post-traumatic stress disorder. Senior author of the study Susumu Tonegawa, 1987 Nobel Laureate and director of the RIKEN-MIT Center, said that, “In animals, traumatic experiences and aging often lead to decline of the birth of new neurons in the dentate gyrus. In humans, recent studies found dentate gyrus dysfunction and related memory impairments during normal aging.”

The study involved the testing of mice in two different types of pattern development memory processes: pattern separation and pattern completion. Pattern separation is the process by which the brain distinguishes between similar events or experiences, such as two hamburgers with different tastes. Pattern completion is used to recall the distinct content of memories based on clues of association surrounding the development of that memory, such as recalling whom one was with during the experience of the hamburger.

So whereas pattern separation forms memories based on differences between similar experiences, pattern completion retrieves memories by discerning similarities. Individuals with brain trauma have trouble recalling people that they see every day, and those with post-traumatic stress disorder are unable to forget disturbing events. Tonegawa explains, “Impaired pattern separation due to the loss of young neurons may shift the balance in favor of pattern completion, which may underlie recurrent traumatic memory recall observed in PTSD patients.”

Neuroscientists thought these two opposing processes occurred in separate neural circuits. Pattern separation was though to be engaged by the dentate gyrus. Pattern completion was thought to occur in the CA3 region. But the study found that dentate gyrus neurons might perform either pattern separation or completion, depending on the age of cells.

Two types of mice were involved in the study: normal mice and those lacking either young or old neurons. During the study, in the portion involving pattern separation, mice were taught to distinguish between two similar chambers. One was “safe” and the other was “unsafe” as it was associated with an unpleasant foot shock. In the portion of the study designed to test pattern completion abilities, mice were given partial cues to escape a maze that they had previously learned to navigate.

Depending on which set of neurons were removed, the mice demonstrated defects in either of the memory pattern processes. Co-author Toshiaki Nakashiba explains their findings in detail, “We found that old neurons were dispensable for pattern separation, whereas young neurons were required for it. Our data also demonstrated that mice devoid of old neurons were defective in pattern completion, suggesting that the balance between pattern separation and completion may be altered as a result of loss of old neurons.”

These findings could lead to a whole new class of drugs aimed at treating memory disorders. The work thus far has been supported by the RIKEN-MIT Center, the Howard Hughes Medical Institute, Ostuka Maryland Research Institute, Picower Foundation and the National Institutes of Health.

Works Cited

“Memory Formation Triggered by Stem Cell Development”. (February 23, 2012). Neuroscience News. February 25, 2012. http://neurosciencenews.com/memory-stem-cells-dentate-gyrus/.

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