A pin to the neurons that can overwrite fear memories
Over the last two years, the world has gone through one of the biggest health crisis associated with a pathogen in recent times. The Covid-19 crisis has been two years of loss, separation, anxiety and uncertainty. Being a frontline worker during the Covid-19 crisis, seeing loved ones pass away from Covid-19, having Covid-19 yourself—these are all traumatic events.
Traumatic events can create memories of fear stored in our brain for a long time, sometimes leading to chronic fear and stress-related conditions such as post-traumatic-stress disorder (PTSD). But how and where these traumatic memories are stored is something that we still do not know exactly. This makes it difficult to understand how we can remove them or attenuate them. In a paper published two years ago in Science, scientists from the École Polytechnique Fédérale de Lausanne (EPFL) dropped a pin to the brain region responsible for storing long-lasting traumatic memories. What was more surprising is that this region is the same involved in making these traumatic memories disappear.
This means that the same neurons storing traumatic memories can help in reprogramming long-lasting memories of traumatic experiences towards memories of safety.
PTSD: a disease that alters brain circuitry and memory organisation
Post-traumatic stress disorder (PTSD) is a mental health condition that's triggered by a terrifying event. PTSD occurs in 5–10% of the population and is twice as common for women than for men.
PTSD affects the circuits in the brain and its chemical composition; this can result in different symptoms including unwanted memories of the traumatic event, flashbacks, nightmares and severe anxiety. In addition to those symptoms it can also induce avoidance of places, activities or people who remind of the traumatic event as well as negative changes in thinking, mood and emotional reactions in the affected.
The diagnosis of PTSD can be challenging because of how different the symptoms can be. The most used therapy against PSTD is exposure therapy, consisting of repetitive exposure to reminders of the original traumatic memory in a safe and controlled environment. Exposure therapy focuses on changing our response to the object or situation we fear.
Short- or Long-Active memories: a matter of location?
Using a fear extinction experiment in mice scientists were able to model what happens -at the cellular level - when long-term memories of trauma are generated, recalled and removed.
First by combining sophisticated tracing methods to create a road map of specific neuronal activity, the team was able to trace neuronal networks involved in storage in traumatic memories. Second using a very thin needle and some chemical compounds or lasers, they managed to turn on and off neurons and consequently modify the mice's behavior.
In an initial experiment they utilized a fear-training exercise producing long-lasting traumatic memories in mice. The team then found that the process of removing fear-related long term memories is different from the one that is involved in removing fear-related short term memories.
Memories over time undergo a process called consolidation, to pass from short term memories to long term memories. This process changes in which neurons and circuits the memories are stored. Through consolidation, over time traumatic memories often become resistant to change.
Nucleus reuniens: a region in the brain that mediates storage and disappearance of fear memories
The team identified that a specific group of neurons in a region called nucleus reuniens were active during the fear-training in mice. When a mouse is scared is it doesn't move anymore. When the mouse goes through a fear-reducing training – emulating exposure-based therapy in humans – the mouse returns to move normally. These nucleus reuniens neurons are involved in storing long-term traumatic memories.
After the treatment of these traumatic memories in the mice, the researchers had a look at the brain again. They observed that the same neurons in the nucleus reuniens remain active. In fact the better the fear extinction work in mice, the more active these neurons in the nucleus reuniens became. When the researchers chemically reduced the activity of these neurons during the fear extinction phase the mice showed less fear reduction and froze more. When they then chemically boosted the activity of these neurons the mice move more, so there was a better fear reduction.
The nucleus reuniens is a region important for the consolidation of long-lasting memories and coordinates the communication between brain areas important for acquisition, recall and consolidation of memory.
Rewriting memories to remove fears
The idea that the neurons involved in acquiring and storing traumatic memories are the same involved in changing these memories to safety is new.
The team's story is that the removal of traumatic memory is not mediated by two distinct memory traces but rather an overwriting of the original memory trace of fear towards safety.
The next step will move from the cell level and go deep into the genetic changes in the neurons during trauma. More importantly to find out if the treatment of the trauma affects those genes.
Knowing exactly what happens during the recalling and treating traumatic memories could help us understand what happened in the human brain and generate better treatment methods. However, as found in animal models, this novel mechanism is still necessary to determine if it occurs in the same way in humans who suffer from PSTD.