Researchers have discovered a DNA modification that enhances our ability to extinguish fear. The findings, published in the journal Nature Neuroscience, could help guide the development of new treatments for fear-related anxiety disorders.
The senior author said while fear is an important survival mechanism which uses cues in the environment to prompt certain responses, so too is the ability to inhibit fear when it's no longer needed. "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," the senior author said.
Fear extinction works as a counter-balance to fear and involves the creation of new non-fearful memories with similar environmental elements that compete with the original fear memory.
The senior author said the balance between fear and fear-extinction is critical to cognitive flexibility, enabling the brain to rapidly adapt to changing conditions. Meanwhile, impairment in fear extinction is a key feature in both post-traumatic stress disorder (PTSD) and phobias.
"Chemical tags on DNA bases act like a dimmer switch that can turn up or turn down the expression of a gene without affecting the underlying DNA sequence," the author said. The team has now discovered how these chemical tags help regulate fear extinction.
"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," another author said.
"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."
The researchers made the discovery by placing mice in a box where they heard a particular tone, which was immediately followed by a mild foot-shock; the mice quickly associated the sound with the foot-shock and froze when they heard it.
To encourage fear extinction, the mice were then placed in a different box, where they repeatedly heard the same sound, but did not receive any foot-shocks. When the mice were returned to the original box, they were no longer afraid of the sound.
The researchers examined the DNA from those mice, particularly the DNA from neurons known to be involved in the fear extinction process. In so doing, they discovered the presence of a modified deoxyadenosine (or adenine) at more than 2800 locations across the genomes of those neurons. They found that this change only occurs during the fear extinction process.
In particular, the team discovered an adenosine modification in a gene called brain-derived neurotrophic factor (BDNF), which is known to nurture learning and memory. Interestingly, the modification appears to increase levels of BDNF during fear extinction.
To confirm the importance of the deoxyadenosine (or adenine) modification to fear extinction, they switched off the gene responsible for making the modification in a group of mice, then repeated the experiment. The mice learned to fear the sound of the tone, but they were unable to form fear extinction memories.
Ultimately, the researchers want to understand the full picture of how fear extinction memory is formed and stored in the brain.
https://qbi.uq.edu.au/article/2019/02/extinguishing-fear-memories-relies-unusual-change-dna
https://www.nature.com/articles/s41593-019-0339-x
Latest News
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Molecular causes of differe…
By newseditor
Posted 16 Apr
Cell's 'garbage disposal' h…
By newseditor
Posted 16 Apr
Other Top Stories
Gene signature could lead to a new way of diagnosing Lyme
Read more
Blood Brain Barrier Crossing by a Parasite
Read more
Inhibitors of bacterial biofilms from natural products
Read more
The right gut microbes help infants grow
Read more
New Ebola-fighting antibodies in blood of outbreak survivor
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Oligodendroglial macroautop…
By newseditor
Posted 17 Apr
COPII with ALG2 and ESCRTs…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar