Scientists have discovered a gene that helps older memories get replaced by new ones.
The gene is critical to the process of memory extinction, the phenomenon where conditioned responses fade away as older memories are replaced with new ones, researchers said.
Enhancing the activity of this gene, known as Tet1, might benefit people with post-traumatic stress disorder (PTSD) by making it easier to replace fearful memories with more positive associations, said Li-Huei Tsai, director of Massachusetts Institute of Technology (MIT)’s Picower Institute for Learning and Memory.
The Tet1 gene appears to control a small group of other genes necessary for memory extinction. “If there is a way to significantly boost the expression of these genes, then extinction learning is going to be much more active,” said Tsai, senior author of the study.
Researchers studied mice with the Tet1 gene knocked out. Tet proteins are very abundant in the brain, which made scientists suspect they might be involved in learning and memory.
The researchers found that mice without Tet1 were perfectly able to form memories and learn new tasks. However, when the team began to study memory extinction, significant differences emerged.
“What happens during memory extinction is not erasure of the original memory. The old trace of memory is telling the mice that this place is dangerous. But the new memory informs the mice that this place is actually safe. There are two choices of memory that are competing with each other,” said Tsai.
In another set of experiments involving spatial memory, the researchers found that mice lacking the Tet1 gene were able to learn to navigate a water maze, but were unable to extinguish the memory.
The researchers found that Tet1 exerts its effects on memory by altering the levels of DNA methylation, a modification that controls access to genes. High methylation levels block the promoter regions of genes and prevent them from being turned on, while lower levels allow them to be expressed.
Many proteins that methylate DNA have been identified, but Tet1 and other Tet proteins have the reverse effect, removing DNA methylation.
The MIT team found that mice lacking Tet1 had much lower levels of hydroxymethylation — an intermediate step in the removal of methylation — in the hippocampus and the cortex, which are both key to learning and memory.