Gene that extinguishes bad memories discovered

Teresa Tanoos's picture
Gene that extinguishes 'brain memory' discovered.
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There is some good news about bad memories: researchers have discovered a gene that can help extinguish painful memories and replace them with new, more positive ones, according to a new study published in the journal Neuron. This could be very good news for those suffering from PTSD or those battling addiction.

Researchers from the Massachusetts Institute of Technology (MIT) say their discovery could help those suffering from post-traumatic stress disorder (PTSD) by replacing "fearful" memories with more positive associations.

Previous research has revealed that the gene, Tet1, plays a crucial role in “memory extinction”, a process that allows the brain to replace negative memories with positive ones.

The Tet1 gene triggers “memory extinction” by controlling a small group of other genes necessary for the process.

For the study, the researchers conducted experiments on mice after they had their Tet1 gene “knocked out”. They also conducted experiments on mice with normal levels of the Tet1 gene.

The mice were then administered a small electric shock to "condition" them to fear a certain. Once the memory of the "cage shock" was formed, the mice were placed into the cage, but the researchers did not give them the shock. This allowed the researchers a way to measure the mice’s ability to “abolish” memories.

After a period of time, they found that mice with normal Tet1 levels seemed to lose their fear of the cage, suggesting that fearful memories could be replaced with new ones.

"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," explained Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory.

However, the research team noted that the mice without the Tet1 gene continued to be fearful and were unable to eradicate the memory.

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Next, the team conducted another set of experiments to test the spatial memory of the mice. As a result, they found that the mice without the Tet1 gene had the ability to learn to navigate a water maze.

However, the mice were unable to extinguish the memory of how to navigate the water maze, further supporting the findings of the previous experiment.

Tet1 and other Tet proteins help regulate the DNA modifications that determine whether a certain gene will be expressed or not.

According to the researchers, Tet1 alters the levels of DNA methylation, a modification that controls access to genes. High methylation levels prevent genes from being expressed, but low methylation levels allow them to be "switched on."

The researchers found that Tet1 and Tet proteins removed DNA methylation – after the mice without Tet1 showed significantly lower levels of hydroxymethylation (the process leading to the removal of methylation, both in in the hippocampus and the cortex of the brain). These regions of the brain are crucial for learning and memory.

Demethylation was found by the researchers to be most significant in a group of 200 genes, particularly a small subset referred to as "immediate early genes" that is crucial for memory formation.

In the mice without the Tet1 gene, they found that immediate early genes were highly methylated. In other words, it would be difficult for these genes to be expressed.

The findings could pave the way for treatments for PTSD.

"By demonstrating some of the ways that regulatory genes are methylated in response to Tet1 knockout and behavioral experience, the authors have taken an important step in identifying potential pharmacological treatment targets for disorders such as PTSD and addiction," said Matthew Lattai, associate professor of behavioral neuroscience at Oregon Health and Science University.

SOURCE: Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction, published in the journal Neuron, 18 September 2013.

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