Are you afraid of the dark? Depending on the circumstances, that fear could safe your life. Perhaps there is a would-be mugger down a dark alleyway, and you chose to take a different path. But you can’t avoid the dark at all times or it would be hard to live. Thus, your brain must counterbalance your fear by engaging in “fear extinction.” During this process, memories are formed during non-fearful experiences with similar environmental elements to your fearful experiences. Then, these non-fearful memories compete with your original fear memory.
The ability to extinguish fearful memories in this way relies on the flexibility of your DNA, specifically Z-DNA, according to a new study. Z-DNA is a counter-clockwise twisted version of B-DNA, the widely recognized double helix. It occurs over short regions and only certain sequences can turn inside-out.
“With a slight rearrangement of how DNA base-pairs connect with one another, DNA can form other helical structures, such as Z-DNA,” explains Paul Marshall, a researcher at the University of Queensland’s Brain Institute and lead author of the study, published in Nature Neuroscience.
While the presence of Z-DNA has been known for some time, scientists only recently discovered that it is a marker of gene activity. Since the formation of fear extinction memories involves rapid changes in gene activity, Marshall wanted to determine if there was a potential link between Z-DNA and memory.
To do this, Marshall and his team focused on an enzyme called ADAR1, which shows an affinity for Z-DNA. It recognizes and latches onto Z-DNA, it is known to play a role in RNA editing, and studies suggest the gene can even convert Z-DNA back into B-DNA. For the study, the researchers turned off the ADAR1 gene in mice, which caused them to lose the capacity for fear extinction. The mice with the gene turned off could still form fear memories, but were unable to form non-fearful memories. The scientists saw similar results when, rather than completely removing the gene, they mutated ADAR1 to be less effective.
These findings suggest Z-DNA forms during fear. Then, during fear extinction, ADAR1 binds to that Z-DNA and carries out two important jobs—it rapidly increases RNA editing and then flips Z-DNA back into B-DNA.
“It seems that the more easily you can switch between DNA structures, the more plastic your memory is,” said Marshall. “Flexibility of DNA structure, flexibility of memory.”
The researchers conclude more research is needed for both fear extinction and Z-DNA. Fear extinction plays a vital role in PTSD and phobias, both of which can be debilitating and life-threatening. The more we understand about the underlying mechanisms of fear extinction, the better chance we have to product effective treatments—treatments soldiers in VA hospitals are depending on.
Beyond fear extinction, scientists have noted high levels of Z-DNA in the brains of people who had Alzheimer’s Disease, and have even connected Z-DNA to certain diseases, including cancer. More and continuing research is necessary.