A team of researchers from The Hospital for Sick Children (SickKids) has uncovered how stress affects the brain’s ability to encode and retrieve memories, particularly in people with post-traumatic stress disorder (PTSD). Their study, published in *Cell*, sheds light on the biological mechanisms behind stress-induced aversive memory generalization, a phenomenon where stress causes memories of a traumatic event to expand and trigger fear responses in unrelated, safe situations. This process can make PTSD symptoms more severe, as individuals react to harmless triggers as though they are threats.
In the study, the researchers explore how stress-induced memory generalization occurs in the brain. Under normal conditions, stress can help individuals respond to challenges and motivate action. However, when stress becomes overwhelming, it can disrupt how the brain forms memories. This leads to a situation where a person with PTSD may experience fear in response to everyday events that are not actually dangerous, such as fireworks or car backfires, even though these triggers have no direct connection to the original trauma.
Dr. Sheena Josselyn, Dr. Paul Frankland, and Dr. Matthew Hill investigated the role of the endocannabinoid system in this process. The endocannabinoid system, known for influencing memory formation and emotional responses, has receptors that help regulate the size and specificity of memory engrams—the brain’s physical representations of memories. The researchers found that stress caused an increase in endocannabinoid release, which in turn disrupted the function of interneurons that usually limit the size of these memory engrams, leading to the formation of larger, more generalized fearful memories.
The study used a preclinical model to replicate the effects of PTSD. In this model, the researchers exposed subjects to acute stress before an aversive event, which resulted in a generalized fearful memory that could be triggered by unrelated, safe situations. The researchers observed that these generalized memories involved significantly more neurons than typical memory engrams, a key indicator of memory distortion caused by stress. This distortion is what underlies the excessive fear responses seen in PTSD.
One promising aspect of the research is the potential therapeutic approach the team identified. By blocking the endocannabinoid receptors on specific interneurons, the researchers were able to prevent the enlargement of memory engrams and reduce the generalization of fearful memories.
This intervention could help alleviate some of the most debilitating symptoms of PTSD by restoring memory specificity and helping individuals better differentiate between safe and dangerous situations. The findings open the door for future therapies that may be able to treat PTSD and similar disorders more effectively, potentially improving the lives of those affected by these conditions.
