An interesting 2015 discovery sheds some light on memory issues:

The urgency to remember a dangerous experience requires the brain to make a series of potentially dangerous moves: Neurons and other brain cells snap open their DNA in numerous locations — more than previously realized, according to a new study — to provide quick access to genetic instructions for the mechanisms of memory storage.

David Orenstein, “Memory-making involves extensive DNA breaking” at MIT News (July 14, 2021) The paper is open access.

Jordana Cepelowicz explains an “unsettling” discovery made by Li-Huei Tsai’s team at MIT’s Picower Institute for Learning and Memory:

… to express learning and memory genes more quickly, brain cells snap their DNA into pieces at many key points, and then rebuild their fractured genome later…

The discovery is all the more surprising because DNA double-strand breaks, in which both rails of the helical ladder get cut at the same position along the genome, are a particularly dangerous kind of genetic damage associated with cancer, neurodegeneration and aging. It’s more difficult for cells to repair double-strand breaks than other kinds of DNA damage because there isn’t an intact “template” left to guide the reattachment of the strands.

Jordana Cepelewicz, “To Learn More Quickly, Brain Cells Break Their DNA” at Quanta Magazine (August 30, 2021)

The unsettling part is that it is not a bug, it is a feature of our brains:

Since then, other studies have demonstrated something similar. One, published last year, associated double-strand breaks not just with the formation of a fear memory, but with its recollection.

Now, in a study last month in PLOS ONE, Tsai and her colleagues have shown that this counterintuitive mechanism of gene expression might be prevalent in the brain. This time, instead of using cultured neurons, they looked at cells in the brains of living mice that were learning to associate an environment with an electric shock. When the team mapped genes undergoing double-strand breaks in the prefrontal cortex and hippocampus of mice that had been shocked, they found breaks occurring near hundreds of genes, many of which were involved in synaptic processes related to memory.

Jordana Cepelewicz, “To Learn More Quickly, Brain Cells Break Their DNA” at Quanta Magazine (August 30, 2021)

One issue the researchers are trying to close in on is memory breakdown during the aging process. The quick memory formation could be at the price of long-term stability:

“We wanted to understand exactly how widespread and extensive this natural activity is in the brain upon memory formation because that can give us insight into how genomic instability could undermine brain health down the road,” says Tsai, who is also a professor in the Department of Brain and Cognitive Sciences and a leader of MIT’s Aging Brain Initiative. “Clearly, memory formation is an urgent priority for healthy brain function, but these new results showing that several types of brain cells break their DNA in so many places to quickly express genes is still striking.”

David Orenstein, “Memory-making involves extensive DNA breaking” at MIT News (July 14, 2021)

Paul Marshall, a University of Queensland researcher whose work has confirmed Tsai’s findings, apoke to Quanta, about that:

Marshall believes that many researchers still have trouble seeing the breaking of DNA as a fundamental regulatory mechanism of gene transcription. “It hasn’t really caught on yet,” he said. “People are still very switched on to the idea of it being DNA damage.” But he hopes his work and the new results from Tsai’s team “will open up the door for other people … to probe a bit deeper.”

Jordana Cepelewicz, “To Learn More Quickly, Brain Cells Break Their DNA” at Quanta Magazine (August 30, 2021) The paper is open access.

Maybe it all just works better when we are young than when we are old.

You may also wish to read some other surprising facts about brain cells:

Study: The human brain and the universe are remarkably similar It looks as though the universe is not random but rather patterned in the way it unfolds. When an astrophysicist and a neurosurgeon compared notes, they were surprised by the way the brain follows the same pattern as the universe.

The human brain has given researchers a big surpise. Gray matter isn’t the big story. Connection—the connectome—is the astonishing feature of the brain. Mapping the “connectome” — all the connections in the brain—researchers expected a huge, random tangle. They found a street map.

Even the axons in our nerve cells are smart PCs Your brain is not a computer, it is billions of them. Contrary to expectations, researchers say, far-flung regions (thousands of cell body widths from their nucleus) can even make independent decisions. (February 15, 2019)

and

“What neuroscientists now know about how memories are born and die” Where, exactly are our memories? Are modern media destroying them? Could we erase them if we wanted to?