Why are painful memories in life so intense

Emotional memories of tragedies in life such as accidents, wars or serious diseases are stored for a long time in the brain. This makes effective treatment difficult. Researchers at ETH Zurich and the University of Zurich have now succeeded in tracking the molecular basis of these strong, persistent memories.

The phrase 'post-traumatic stress disorder' is a permanent phrase of all referring to those returning from the Iraq war or victims of disasters such as tsunamis. This is not a new development because it always happens to people who experience extremely difficult situations. Everyone knows that both positive and negative emotional memories are stored by the brain for a long time.

As a result, these memories have a huge impact on our behavior and in the case of harmful memories, they can hinder the way we return to life. As a result, we avoid places, smells or objects that recall painful memories because they cause serious anxiety. Isabelle Mansuy, Professor of cellular neuroscience at ETH Zurich and Cell and Cognitive Neuroscience at the University of Zurich, has now demonstrated that the enzyme calcineurin and the gene regulation factor Zif268 determine the intensity of emotional memories. For the first time, this helps scientists link the synaptic coordination process, which is important for emotional memory, with the process in the cell nucleus.

In their experiments, the researchers trained rats to associate sugar with vomit.This training takes place for several months.Mice avoid sugar water during this time.(Photo: ETH Zurich)

Experiments on mice

The production of the most durable memories in the shortest possible time requires molecules in the brain, which are not only activated quickly but also effectively control the signaling process of long-term information storage. long in the brain. This is why the protein phosphatase calcineurin, known to have a negative coordination effect on learning and memory, is a promising candidate for Zurich researchers. They use mice as a model system because their learning process is very similar to humans and established behavioral tests exist. In their experiments, the researchers trained rats to associate sugar with vomit. This training takes place for several months. Mice avoid sugar water during this time.

However, aversion can be overcome gradually by intense training. Mansuy explained that 'Emotional memories are not easy to erase. Heavy negative memories need to be proactively replaced by positive memories. ' She said it is important that at the same time understand that negative memories do not disappear, they merely slip down in the priority list and get overtaken by positive memories. 'This process is not final and absolute, because the priority list can change again.'

Karsten Baumgärtel, a postdoctoral researcher in Mansuy group, emphasized that this is a big difference between emotional memories and knowledge.'Events can disappear from memory completely, on the contrary in some special cases that recreate emotions stored throughout life. Intentional intervention is necessary to reduce the priority of negative memories. '

Calcineurin depletion activity

The study of amygdala (amygdala), the brain region important for emotional perception, shows the decline in activity of calcineurin enzymes in experimental mice compared to normal mice.Because calcineurin is a negative coordinator for learning and memory, its activity needs to be limited to enhance memory . To gain more evidence about the role of calcineurin in memory, scientists used genetically modified mice that could activate or eliminate selective enzymes in brain neurons. Mansuy explained that 'Selective activation and reduction in neurons is important because calcineurin is an enzyme present in many cells.'

For example, it also plays an important role in the immune system. According to the researchers, the reduction of calcineurin activity boosts the memory associated with sugar and vomit, while memory declines with increased calcineurin activity. Researchers can also demonstrate that the time needed to reduce negative memory by positive memory alone can be prolonged or shortened by this intervention.

The process of coordination in synapses and cell nuclei

Inactivation of calcineurin also causes a decrease in Zif268 gene coordinator in the amygdala region. Zif268 is responsible for coordinating a series of important genes that play a role in signal processing of memory and learning.This stimulant enhances Zif268 expression in genetically modified mice to boost memory in a way similar to calcineurin reduction . This is the first time it has been possible to demonstrate the importance of functional relationships between the activity of an enzyme in the synapse and the activity of the gene regulation factor in the cell nucleus.

Mansuy and Baumgärtel emphasize that the purpose of their research is to gain a basic knowledge of molecular relationships, but this does not involve any direct medical applications in the near future. .

However, Mansuy explained, 'In the past, the origins of many diseases were mysterious and they were thought to be God's punishment, and at that time the infected people came to the monks. Today we understand some of the mechanisms within them and can cure these diseases. We hope this work contributes a small part to realizing the same situation that also applies to the future for psychological trauma or brain impairments such as Alzheimer's, Parkinson's and stroke. . '