Researchers sucessfully make memories stronger and more precise during aging in mice.


It is known that neurons in the central nervous system of higher vertebrates are formed during embryonic development and that neurogenesis does not occur postnatally, except in the hippocampus. Buried deep underneath the folds of the cerebral cortex, neural stem cells in the hippocampus continue to generate new neurons, inciting a struggle between new and old, as the new attempts to gain a foothold in memory-forming center of the brain.  Now, a study from researchers led by Harvard Stem Cell Institute (HSCI) shows it is possible to bias the competition in favour of the newly-generated neurons. The team state that the hippocampus allows humans to form new memories of ‘what, when and where’ which help them navigate their lives, and neurogenesis, the generation of new neurons from stem cells, is critical for keeping similar memories separate.  The study is published in the journal Neuron.

Previous studies show that 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 current study shows that rejuventation of the hippocampus by enhancing integration of adult-born neuron stem cells, otherwise known as granule cells, in adulthood, middle age, and aging enhanced, memory precision.

The current study selectively over expressed the 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.  Results show that when the expression of Klf9 was returned back to normal, the old dendritic spines reformed, restoring competition, however, the previously integrated neurons remained.

The lab explain that because this can be done in reverse at any point in an animals life, the hippocampus can be rejuvenated with extra, new, encoding units. They go on to add that to achieve this they employed a complementary strategy in which a protein, Rac1, was deleted which is important for dendritic spines, only in the old neurons and achieved a similar outcome, increasing the survival of the new neurons.

The researchers state that in order to keep two similar memories separate, the hippocampus activates two different populations of neurons to encode each memory in a process called pattern separation.  They go on to add that when there is overlap between these two populations, it is believed to be more difficult for an individual to distinguish between two similar memories formed in two different contexts.

The group explain that if the memories are encoded in overlapping populations of neurons, the hippocampus may inappropriately retrieve either.  They go on to add that if the memories are encoded in non-overlapping populations of neurons, the hippocampus stores them separately and retrieves them only when appropriate.  The researchers observed that mice with increased neurogenesis had less overlap between the two populations of neurons and had more precise and stronger memories, which demonstrates improved pattern separation.  They conclude that mice with increased neurogenesis in middle age and aging exhibited better memory precision.

The team surmise that their findings suggest by increasing the hippocampus’s ability to do what it is supposed to do and not retrieve past experiences when it shouldn’t, can help. For the future, the researchers state that this may be particularly useful for individuals suffering from post-traumatic stress disorder, mild cognitive impairment, or age-related memory loss.

Source: Harvard Stem Cell Institute (HSCI) 

 

Young neurons (pink), responsible for encoding new memories, must compete with mature neurons (green) to survive and integrate into the hippocampal circuit. Photo courtesy of Kathleen McAvoy, Sahay Lab.

Young neurons (pink), responsible for encoding new memories, must compete with mature neurons (green) to survive and integrate into the hippocampal circuit. Photo courtesy of Kathleen McAvoy, Sahay Lab.

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