When we think of the double helix that is DNA, we tend to only think there is one orientation to the way that DNA faces, twisting clockwise. There is another conformation of DNA which faces outward and twists counterclockwise, and some of the answers in how the brain recognizes fear and fear memories lies within this alternative orientation.
The DNA which twists clockwise is referred to as B-DNA. Z-DNA is formed when the base pairs of the DNA structure are rearranged and forms a different structure, still helical. Scientists have been aware of Z-DNA and knew it only forms over short regions. They knew that it seemed to mark where genes were being activated, but it wasn’t clear why it happened.
The newest paper published by Professor Tim Bredy of the Queensland Brain Institute in the journal Nature Neuroscience finds a reason for Z-DNA that involves the ability to let go of fearful memories, dependent on how flexible your DNA can be.
As well as being involved in releasing fearful memories, Z-DNA has been found in diseases, such as cancer and in the brains of Alzheimer’s Disease patients.
To explore how memory is tied to Z-DNA, Professor Bredy’s research team focused on the enzyme which attaches itself onto Z-DNA after it is recognized. This enzyme, ADAR1, converts Z-DNA back to the B-DNA formation.
Studying ADAR1 in the brains of mice, they found it in the area of the brain where fear is quelled. When the ADAR1 was turned off, the mice could only form fearful memories. ADAR1 is directly linked to being able to suppress and extinguish fear. Based on these findings, it appears that Z-DNA forms during fear and when the fear is extinguished, the ADAR1 binds to the Z-DNA and returns it to its B-DNA form.
Based on this, they believe that fear memories were meant to be plastic and flexible so that once they have served their purpose, your brain can quell the fear memory and move past it. The key to being able to switch between Z-DNA and B-DNA is based on the plasticity of your memory, and this can hold a lot of answers in being able to help people who are unable to properly perform the process of fear extinction.
Fear extinction is an integral part in being able to progress through certain psychological disorders, such as PTSD and fear-based phobias. Those that are affected by not being able to properly extinguish the fears once the moment has passed find that their fears interfere with normal daily functioning. It is promising that in the future it may be possible to work with the ADAR1 gene further and develop treatments which can improve the transitions from Z-DNA back into B-DNA and help people achieve better fear memory plasticity.
Marshall, Paul R., et al. “Dynamic Regulation of Z-DNA in the Mouse Prefrontal Cortex by the RNA-Editing Enzyme Adar1 Is Required for Fear Extinction.” Nature Neuroscience, 4 May 2020, https://www.nature.com/articles/s41593-020-0627-5.