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April 2024
Researcher: Shaenette Louisa
Editor: Alice Pham
In a recent study by Jelena Radulovic and her team, researchers found that during the process of long-term memory formation, certain brain cells experience a powerful rush of electrical activity leading to breaks in double-stranded DNA. This activates an inflammatory response which repairs the damaged DNA and solidifies the memory in the brain. Under normal circumstances, double-strand breaks are linked to diseases like cancer because their repair can result in mutations and chromosomal rearrangements due to non-homologous DNA end joining, the primary repair pathway for double-strand breaks. However, this study suggests that this cycle of destruction and repair may explain our memory formation and maintenance.
Despite the recent discovery, the connection between memory and DNA has been explored before. Such as in a past experiment that showed the prevalence of double-stranded DNA breaks in the brain and linked them to learning.
In the current study, Radulovic and her colleagues trained mice to associate mild electric shocks with new environments. After analyzing gene activity in neurons within the hippocampus, a region of the brain that deals with memories, they found that this training appeared to induce memory formation, as the mice reacted fearfully when placed in the same environment where they had been shocked. After a few days, they also found that particular inflammation-related genes were active in a subset of neurons; however, examination after three weeks revealed that their activity had significantly diminished.
The source of this inflammation stems from TLR9, a protein known to trigger an inflammatory response to genetic material in cells, similar to the response used against foreign invaders. TLR9 exhibited the most activity in a subset of neurons in the hippocampus, where DNA breaks resistant to repair were detected. Within these neurons are machinery that repairs DNA accumulates in centrosomes, organelles associated with cell division and differentiation. Considering fully developed neurons do not perform cell division, Radulovic theorizes that neurons record data about triggering events during damage and repair cycles.
This is supported by the behavior of mice lacking the TLR9 encoding gene, as they had difficulty recalling long-term memories and froze less often compared to unaltered mice. This suggests that DNA serves as a signal to retain information over extended periods and raises the possibility that individuals diagnosed with neurodegenerative diseases may have a faulty damage and repair cycle, causing the accumulation of errors in neuron DNA.
It remains to be determined how these results relate to other memory-related discoveries, such as engrams, which are a group of hippocampal neurons that function as a physical record of memories. The researchers note that the subset of neurons linked to inflammation differs from those in the engram production. However, Tomás Ryan, an engram neuroscientist from Trinity College, hypothesizes that the DNA damage and repair cycle may result from the formation of engrams rather than the subset of neurons examined recording something unique.
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