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Memory Formation Requires Extensive DNA Breakage In The Brain


Ben Taub

Freelance Writer

clockJul 9 2021, 15:49 UTC
DNA break

DNA breakage occurs in multiple types of brain cell during memory formation. Image: Anusorn Nakdee/

In order to rapidly encode new memories, neurons and other types of brain cell must alter their behavior in real-time. Doing so requires certain genes to become upregulated at a moment’s notice, and new research indicates that this process relies on both strands of DNA snapping open at numerous locations, thereby allowing key genetic instructions to be read instantly.

Appearing in the journal PLoS One, the new study implies that this continual breaking of genetic material in the brain may play a role in age-related cognitive decline, as the mechanisms by which these breakages are repaired can become less efficient as we get older, resulting in neurodegeneration.


The study builds previous research which showed that neurons grown in petri dishes undergo double strand breaks (DSBs) in a limited number of gene location as they carry out certain functions. To investigate the scope of this effect in vivo, the researchers trained mice to develop a conditioned fear memory by repeatedly applying mild electric shocks to their feet.

They then profiled the DSBs that occurred in the animals’ hippocampi and prefrontal cortices, both of which are central to learning and memory. Results showed that DSBs occur in hundreds of gene locations as memories are forming, with the study authors expressing surprise at the number of DNA breakages that they saw.

“Previously, we observed 20 gene-associated [DSB] loci following stimulation of cultured neurons, while in the hippocampus and prefrontal cortex we see more than 100–150 gene associated [DSB] loci that are transcriptionally induced,” write the researchers.


Many of these DSBs affected genes that are involved in synaptic plasticity, which refers to the brain’s ability to form new neuronal connections. This would make sense, given that the establishment of new memories relies upon the creation of new groups of brain connections. Accordingly, the researchers detected an increase in the expression of large numbers of genes involved in synaptic function within the first half hour after each round of foot shock exposure.

In another surprising twist, the team also noted large numbers of DSBs in brain cells other than neurons, with glia – the brain’s support cells – also displaying significant DNA breakage in response to the establishment of conditioned fear memories. A deeper analysis revealed that many of the DSBs that occur within glia affect genes that are involved in the regulation of glucocorticoid receptors.

Glucocorticoid is a hormone that is secreted in response to stress, so the fact that it appears to be involved in the formation of fear-based memories comes as little surprise.


Overall, the study authors say that the sheer scale of DSBs that are required for memory consolidation, coupled with the fact that they occur in multiple types of brain cell, radically alters our understanding of the neurological underpinnings of memory.

They go on to state that these breakages must be rapidly repaired via a process called non-homologous end joining, and that any errors that occur during this process could result in an “accumulation of irreversible sequence damage with time [that] has the potential to perturb brain function during aging and disease.”

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