Stress alters memory formation by creating larger neural “engrams,” making it harder for individuals to differentiate between harmless and fearful situations. Researchers discovered that this process occurs in the amygdala, and their findings may offer insights into treating conditions like PTSD. The study also explores potential drug interventions to reverse stress-induced memory changes.
By PC Bureau
New Delhi
Stress causes mice to form larger bundles of neurons in the brain, which disrupt memory formation and make them fearful of harmless situations. This may help explain why people under stress often feel threatened in otherwise safe environments. Researchers have long known that stress and trauma can cause people to fear benign situations—such as avoiding not only a hot pan after burning a finger, but the kitchen itself. This generalized fear is common in conditions like post-traumatic stress disorder (PTSD) and generalized anxiety disorder.
A recent study published in Cell and reported in Nature highlights how stress impairs memory, particularly the recall of fearful events. These findings could lead to new therapies for PTSD and anxiety disorders.
Sheena Josselyn, a neuroscientist at the Hospital for Sick Children in Toronto, and her team explored how stress affects memory formation in the brain. They focused on the amygdala, a region linked to stress and emotional responses, and its role in creating “engrams”—neural clusters that store memories.
In an experiment with mice, the researchers stressed some by injecting them with corticosterone or restraining them in a tube. Afterward, they exposed the mice to neutral and fearful events: first, a neutral sound followed by a high-pitched whistling sound paired with a foot shock. They then tested the mice’s memory by exposing them to these sounds in a new environment.
The unstressed mice reacted by freezing to the fearful sound, but the stressed mice froze to both sounds, unable to distinguish between neutral and fearful events. This suggested that stress had caused them to form larger engrams.
Further investigation revealed how stress causes these larger engrams. Under normal conditions, neurons in the amygdala release gamma-aminobutyric acid (GABA) to limit the formation of large engrams. But stress disrupts this process, allowing more neurons to form larger engrams by interfering with the GABA release. Essentially, the “velvet rope” that normally restricts access to the neural “club” is removed.
The researchers found that by using two drugs—one of which is mifepristone, typically used for early pregnancy termination—they could reverse the stress-induced memory changes in mice. These drugs block the stress-related pathways and restored the smaller, more specific engrams. However, the drugs only work if administered at the time the memory is formed and have side effects beyond the brain, so they are not suitable for human treatment.
Josselyn’s team is now exploring ways to alter engrams after memories have been formed or develop alternative methods to reduce the impact of stress on memory.
