MIT Study Finds Making Memories Requires Extensive DNA Breaking

Researchers at MIT have published an interesting study involving how we make memories. The study says quickly expressing learning and memory genes requires brain cells to snap both strands of DNA in many more places and cell types than previously realized. Neurons and other cells inside the brain break open their DNA in numerous locations to provide quick access to genetic instructions for the mechanisms of memory storage.

The extent of the DNA double-strand breaks (DSBs) in multiple key regions of the brain is both surprising and concerning, according to the senior author of the study Li-Huei Tsai. Tsai says that while these breaks are repaired routinely, the process could become more flawed and fragile as we age. In the lab, Tsai has shown that lingering DSBs are associated with neurodegeneration and cognitive decline due to repair mechanisms that falter.

Researchers want to understand how widespread and extensive the natural activity of breaking DNA in the brain is on memory formation to give an insight into how genomic instability could undermine brain health in the future. In the new study, researchers investigated the full landscape of DSB activity in learning and memory. To do so, they gave mice small electrical shocks to their feet when they enter a box to condition a fear memory of that context.

Then the team used methods to assess DSBs and gene expression in the brains of the mice over the preceding half-hour, particularly among cells in the prefrontal cortex and hippocampus, which are regions essential for the formation and storage of conditioned fear memories. They perform the same measurements in the brains of mice that didn't experience the shock for baseline.

They found the creation of a fear memory doubled the number of DSBs among neurons in the hippocampus in the prefrontal cortex, impacting more than 300 genes in each region. Many of the genes are associated with the function of connections neurons make with each other, called synapses. Overall, the team found that transcriptional changes are more strongly associated with DSBs in the brain than anticipated. The team does say additional research is needed to prove DSBs required for forming and storing fear memories are a threat to brain health later.