Researchers found that Tension It changes how our brain encodes and retrieves aversive memories. They also developed a potential new method to restore adequate memory specificity in individuals suffering from post-traumatic stress disorder (PTSD). The researchers were from The Hospital for Sick Children (SickKids).

Dr. Sheena Joslin and Paul Frankland, senior scientists in the Neurosciences and Mental Health Program, identify the biological processes behind stress-induced aversive memory normalization and highlight an intervention that may help restore proper memory specificity for people with PTSD. Can help.

Jocelyn, who holds the Canada Research Chair in the Circuit Basis of Memory, said, “A little bit of stress is good, it’s what gets you up in the morning when your alarm goes off, but too much stress can be debilitating.

“We know that people with PTSD show fearful responses to safe situations or environments, and they have found a way to limit this fearful response in specific situations and potentially reduce the harmful effects of PTSD.”

Together with their collaborator Dr. Matthew Hill at the University of Calgary Hotchkiss Brain Institute, the research team was able to block endocannabinoid receptors on interneurons and limit stress-induced aversive memory generalization to specific, appropriate memories.

In a preclinical model, the research team exposed subjects to an intense, but safe, stressor before an adverse event to create a non-specific fear memory, which can be triggered by unrelated safe situations, similar to PTSD in humans.

The team then examined the subject’s memory engram, a physical representation of memory in the brain, developed by the Joslin and Frankland laboratories at SickKids. Typically, engrams are composed of a small number of neurons, but stress-induced memory engrams involve significantly more neurons. These large engrams generated generalized fear memories that were retrieved even in safe situations.

When they looked closer at these larger engrams, the study found that stress caused an increase in the release of endocannabinoids (endogenous cannabinoids), which disrupted the function of interneurons, whose role is to limit the size of the engram.

The endocannabinoid system enhances memory formation and helps associate lived experiences with specific behavioral outcomes. In the amygdala, the brain’s emotional processing center, some ‘gate keeper’ interneurons have specialized receptors for endocannabinoids and help limit the size of engrams and the specificity of memory. But, when too many endocannabinoids are released, the function of gatekeeping interneurons is disrupted, causing the engram to increase in size.

Jocelyn explains, “Endocannabinoid receptors work like a velvet rope in a special club. When stress induces the release of too many endocannabinoids, the velvet rope collapses, creating more generalized aversive fearful memories.

“By simply blocking these endocannabinoid receptors on these specific interneurons, we can essentially prevent one of the most debilitating symptoms of PTSD.”

In 2023, previous research in Science identified larger, more generalized memory engrams, like stress-induced memory engrams, in the developing brain compared to the adult brain. As they continue to explore this unexpected relationship between engram size, stress, and age, the teams are also exploring how daily stressors may affect pleasant memories.

“Many of the biological functions and processes that make up the complexity of human memory are still being unraveled,” said Frankland, who holds the Canada Research Chair in Cognitive Neurobiology. We hope that as we better understand human memory, we can inform real-world treatments for people suffering from various psychiatric and other brain disorders across the lifespan.

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