Fear is a vital survival tool, but when it gets too extreme or sticks around long after the trigger, it can really get in the way of someone's day-to-day life. New research from the University of Queensland (UQ) in Australia has now found a chemical pathway that helps the brain wipe fear memories, which could lead to new potential treatments for phobias and other fear-related anxiety disorders.
On the opposite end of the seesaw to fear sits fear extinction. While it's crucial to develop a fear of something that might be dangerous, the brain needs to be able to overwrite those fear memories if it's no longer a concern. Finding the right balance between fear and fear extinction is important, and problems with this mechanism can crop up as debilitating phobias, PTSD or other anxiety disorders.
"You still want to have that memory of 'there's something dangerous there, I want to be careful,' but you don't want it to compromise your ability to function normally," says Timothy Bredy, an author of the new study.
The UQ team has now identified a DNA modification that seems to boost fear extinction. In tests, the researchers first taught mice to associate a specific tone with a mild electric shock. Understandably, they soon became afraid of the tone itself and would freeze when they heard it.
Next the researchers moved the mice to a different box, where they played the tone repeatedly without giving them shocks. When the mice were then moved back to the original box, they had learned not to fear the sound anymore.
So far this sounds like regular old "exposure therapy," where a patient is exposed to the thing they're afraid of until they become desensitized to it. While that's reasonably effective, it's not the most pleasant process and can often result in relapses down the track. This study instead looked at what's going on in the brain during this process, in order to perhaps find a way to mimic the benefits without the actual exposure to the trigger.
To this end, the team examined the mice to see if the experiments had changed their DNA in any way. And sure enough, in the neurons responsible for the fear extinction process, they found over 2,800 instances where the DNA base adenine had been chemically tagged to change gene expression. In particular, it seems like these modifications were ramping up activity in a gene called brain-derived neurotrophic factor (BDNF), which is associated with learning and memory.
"For a long time, it was thought that only one DNA base – cytosine – could be modified, and that these chemical changes in the brain reduce gene expression," says Xiang Li, an author of the study. "We have now discovered that adenosine, another DNA base, can also be chemically tagged, and that fear extinction memories form thanks to a deoxyadenosine (or adenine) modification that increases the activity of certain genes."
To confirm the role that these modifications were playing in the fear extinction process, the team then engineered mice that didn't have the ability to make that DNA modification. After repeating the experiment, these mice also learned to fear the sound but couldn't undo the process, remaining scared of the tone long after the threat of the shocks had passed.
The researchers say this could unlock a new potential target for treating anxiety disorders in humans. While any such benefit to us would still be a long way off, this study is just one of many examining how fear functions in the brain. Similar recent work has found that fears could be fought by retraining the brain to associate bad cues with rewards instead, or reducing anxiety by magnetically stimulating the brain.
The research was published in the journal Nature Neuroscience.
Source: University of Queensland
