Why are frightening memories so hard to forget?

The ability to experience fear is essential to escape from life-threatening situations and to learn how to avoid them in the future. However, in some illnesses, such as post-traumatic stress disorder and other anxiety-related disorders, fear reactions become excessive and persist even when they are no longer appropriate. This triggers intense anxiety even though the danger is no longer present, and leads to the impossibility for the affected person to lead a normal life until their disorder ceases. It is suspected that certain individuals have a greater tendency to develop pathological fears, and that this is due to disorders in the way the brain processes memories of frightening things.

Some areas of the brain are especially important for processing fear-related memories. The amygdala is activated when threats are experienced, and works in conjunction with parts of the frontal lobes of the brain, the “prefrontal cortex,” that are important for regulating emotions.

The network of nerve cells connecting the frontal lobes to the amygdala is known to be involved in managing fear. The connections between these brain structures are altered in people with post-traumatic stress disorder and other anxiety disorders.

However, the molecular mechanisms involved have been unknown for a long time.

In a new study, Estelle Barbier’s team at Linköping University in Sweden investigated a protein known as PRDM2, an epigenetic enzyme that suppresses the expression of many genes. The researchers had already found that PRDM2 levels are lower in individuals who are dependent on alcohol, leading to exaggerated stress responses. Many people with alcohol dependence often also suffer from anxiety, and researchers have long suspected that this is because both problems are regulated by a common mechanism.

The research team, including Riccardo Barchiesi and Estelle Barbier, have discovered a biological mechanism that increases the strength with which frightening memories are stored in the brain. (Photo: Anna Nilsen / Linkoping University)

For new memories to last, they must be stabilized and preserved as long-term memories. This process is known as “consolidation.” The authors of the new study investigated, in rats, the effects of reduced levels of PRDM2 on the way memories of frightening events are processed.

And they have verified that the reduction of PRDM2 increases the consolidation of memories related to fear. Specifically, reduced levels of PRDM2 lead to increased activity in the network between the frontal lobes and the amygdala, which in turn intensifies learned fear reactions.

The researchers have also identified the genes that are affected when the level of PRDM2 is reduced.

In short, the result of all this is an increase in the activity of the nerve cells that connect the frontal lobes and the amygdala.

The study is titled “An epigenetic mechanism for over-consolidation of fear memories.” And it has been published in the academic journal Molecular Psychiatry. (Font: NCYT by Amazings)