Researchers have tracked down genes within mice that help soothe fear-related memories. We had written off these genes asjunk DNA, but they are hidden in relatively unknown regions.
It is like using the power of the Hubble Telescope to peer into the unknown of the brain, according to University of Queensland neuro Epigeneticist Timothy Bredy.
15 million people in the US are affected by fear disorders such as phobias and post-traumatic stress disorder.
We all have memories that scare us and make us avoid certain situations. This is a learning response that keeps us safe.
In normal situations, repetitive exposure to these fear cues, without anything bad happening, should decondition your fear response.
The fear and extinction of it takes place in the brain's prefrontal cortex, and recent research shows that the process is caused by alterations to the genes in our genomes.
Some of us never get that downregulation of fear.
The fears become a mind-killer that prevents our brains from letting us deal with these things rationally or move on from the fearful events.
Using fear-conditioned mice, researchers looked at long noncodingRNA that has already been implicated as regulating genes linked to conditions such as drug addiction, depression, and schizophrenia. Forty percent of the lncRNA identified so far is found within the brain.
The researchers found a class of genes that are expressed in the mice's prefrontal cortex, which is involved in linking our experiences to regulation of gene expression.
One gene, dubbed ADRAM (activity dependent lncRNA associated with memory), appears to work both as a scaffold that allows other molecule access to a gene for its expression and to coordinate other molecule, including eRNAs, that express a gene which helps dull fears.
When the expression of ADRAM was knocked out in the mice before they were deconditioned of their fear, they showed no difference within their fear downregulation training sessions compared to the controls.
The knockout mice remained fearful, suggesting their fear extinction memory was impaired. Their fear and anxiety behaviors were normal.
The researchers wrote in their paper that the effect of the gene knockouts on fear extinction is due to their influence on cognitive functioning.
The team cautions that they don't know if ADRAM plays a more extensive role in learning and only found the effects on male mice. This class of lncRNA genes deserves a closer look because many of them are conserved across species.
According to our findings, long non-codingRNAs provide a bridge, linking dynamic environmental signals with the mechanisms that control the way our brains respond to fear.
With this new understanding of gene activity, we can now work towards developing tools to target long non-coding RNAs in the brain that directly modify memory and hopefully, develop a new therapy for post-traumatic stress disorder.
Cell Reports published this research.
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