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Brain Health

Keeping New Memories Separate from Old Ones as We Age

The hippocampus, the memory-forming center of the brain, generates new neurons throughout our lives. As time goes by, the older neurons compete with the new ones so that we sometimes remember a long ago event at the same time as we remember a more recent event if the triggers are similar. An example of this phenomenon, according to a release from Harvard Medical School regarding a study published online in September 2016 in Neuron, is having difficulty discriminating between a Sunday afternoon stroll through the woods and a patrol through enemy territory in a forest. That, needless to say, could result in an episode of PTSD.

The study, done by Harvard Stem Cell Institute (HSCI) researchers at Massachusetts General Hospital and the Broad Institute of Harvard and MIT in collaboration with an international team of scientists, found that the researchers could bias the competition in favor of the newly generated neurons.

A release from Harvard Medical School quotes HSCI Principal Faculty member and the study’s corresponding author, Amar Sahay, PhD as saying, “The hippocampus allows us to form new memories of ‘what, when and where’ that help us navigate our lives, and neurogenesis–the generation of new neurons from stem cells–is critical for keeping similar memories separate.”

As the human brain matures, the connections between older neurons become stronger, more numerous, and more intertwined, making integration for the newly formed neurons more difficult. Neural stem cells become less productive, leading to a decline in neurogenesis. With fewer new neurons to help sort memories, the aging brain can become less efficient at keeping separate and faithfully retrieving memories.

The research team selectively overexpressed a transcription factor, Klf9, only in older neurons in mice, which eliminated more than one-fifth of their dendritic spines, increased the number of new neurons that integrated into the hippocampus circuitry by two-fold, and activated neural stem cells.

When the researchers returned the expression of Klf9 back to normal, the old dendritic spines reformed, restoring competition. However, the previously integrated neurons remained.

“Because we can do this reversibly, at any point in the animals life we can rejuvenate the hippocampus with extra, new, encoding units,” Sahay said.

The authors employed a complementary strategy in which they deleted a protein important for dendritic spines, Rac1, only in the old neurons and achieved a similar outcome, increasing the survival of the new neurons.