Your Brain Breaks Its Own DNA To Form Memories That Can Last A Lifetime

A new study in mice suggests that breaking and repairing DNA in neurons paves the way for long-lasting memories. We form memories when electrical signals zap through neurons in the hippocampus, a seahorse-shaped region deep inside the brain. The electrical pulses wire groups of neurons together into networks that encode memories.

The new study found a subset of neurons that alter their connections to encode long-lasting memories.

“Inflammation of brain neurons is usually considered to be a bad thing, since it can lead to neurological problems such as Alzheimer’s and Parkinson’s disease,” said study author Dr. Jelena Radulovic at Albert Einstein College of Medicine in a press release.

“But our findings suggest that inflammation in certain neurons in the brain’s hippocampal region is essential for making long-lasting memories.”

He retained old memories, but could no longer form new ones, suggesting that the brain region is a hotspot for encoding memories. What does DNA have to do with the hippocampus or memory?

Depending on the signals, synapses can form a strong connection to their neighboring neurons, or they can dial down communications.

Scientists have long thought it’s the basis of memory. In the hippocampus, this “Dial” can rapidly change overall neural network wiring to record new memories. With new learning, electrical signals from neurons cause temporary snips to DNA inside neurons. It’s been associated with memory formation since 2021.

One study found breakage of our genetic material is widespread in the brain and was surprisingly linked to better memory in mice.

After learning a task, mice had more DNA breaks in multiple types of brain cells, hinting that the temporary damage may be part of the brain’s learning and memory process. To find an answer, the team used a standard method for assessing memory.

Here the gene became highly active in neurons inside the hippocampus-especially those with persistent DNA breaks that last for days.

When challenged with the chamber test, these mice struggled to remember the “Dangerous” chamber in a long-term memory test compared to peers with the gene intact.

Deleting the gene prevented mouse cells from recognizing DNA breaks, causing not just loss of long-term memory, but also overall genomic instability in their neurons.

“One of the most important contributions of this study is the insight into the connection between DNA damageand the persistent cellular changes associated with long-term memory,” wrote Kelvington and Abel.

In 2021, the same team found that net-like structures around neurons are crucial for long-term memory.

The new study pinpointed TLR9 as a protein that helps form these structures, providing a molecular mechanism between different brain components that support lasting memories.

The results suggest “We are using our own DNA as a signaling system,” Radulovic told Nature, so that we can “Retain information over a long time.”

Does DNA damage predispose certain neurons to the formation of memory-encoding networks? And perhaps more pressing, inflammation is often associated with neurodegenerative disorders, such as Alzheimer’s disease.

“How is it that, in neurons, activation of TLR9 is crucial for memory formation, whereas, in microglia, it produces neurodegeneration-the antithesis of memory?” asked Kelvington and Abel.

“What separates detrimental DNA damage and inflammation from that which is essential for memory?”.