Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory, along with his team studied mice with the Tet1 gene knocked out. Tet1 and other Tet proteins help regulate the modifications of DNA that determine whether a particular gene will be expressed or not.
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.
To measure the mice's ability to extinguish memories, the researchers conditioned the mice to fear a particular cage where they received a mild shock. Once the memory was formed, the researchers then put the mice in the cage but did not deliver the shock. After a while, mice with normal Tet1 levels lost their fear of the cage as new memories replaced the old ones.
"What happens during memory extinction is not erasure of the original memory," Tsai said. "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."
In normal mice, the new memory wins out. However, mice lacking Tet1 remain fearful.
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 findings suggest that a threshold level of methylation is necessary for gene expression to take place, and that the job of Tet1 is to maintain low methylation, ensuring that the genes necessary for memory formation are poised and ready to turn on at the moment they are needed.
The study is published in the journal Neuron.