How stress is drastically changing our memories
In order to restore proper memory specificity in individuals with post-traumatic stress disorder (PTSD), researchers at The Hospital for Sick Children (SickKids) discovered that stress changes how our brain encodes and recovers negative memories.
Your brain may link your next presentation to that one bad and unpleasant experience, which could make you anxious the next time you have to give a presentation. One memory is linked to this kind of stress.
A phenomenon known as stress-induced unpleasant memory generalization occurs when stress from traumatic events, such as violence or generalized anxiety disorder, spreads far beyond the initial incident. For example, fireworks or automobile backfires might cause fearful memories that seem unconnected and ruin your entire day.
It can have far more detrimental effects in the case of PTSD.
Sheena Josselyn and Paul Frankland, senior scientists in the Neurosciences & Mental Health program, describe the biological mechanisms underlying stress-induced aversive memory generalization in a study that was published in Cell. They also highlight an intervention that may help PTSD sufferers regain appropriate memory specificity.
A Canada Research Chair in Circuit Basis of Memory, Josselyn adds, "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 have found a way to limit this fearful response to specific situations and potentially reduce the harmful effects of PTSD."
The study team and their colleague Matthew Hill from the University of Calgary Hotchkiss Brain Institute were able to limit stress-induced painful memory generalization to the relevant memory by blocking endocannabinoid receptors on interneurons.
The study team used a preclinical model in which participants were exposed to an acute but safe stress before an aversive event in order to create a non-specific terrified memory that may be triggered by unrelated safe settings, similar to how PTSD occurs in humans.
The team subsequently investigated the subject's memory engrams, the physical traces of memories in the brain initially developed by the Josselyn and Frankland labs at SickKids.
Typically, engrams consist of a small number of neurons; however, stress-induced memory engrams engage a substantially larger number of neurons. These larger engrams produced generalised fearful memories that were retrieved even in safe situations.
When they looked closer at these large 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 it to constrain the size of the engram.
The endocannabinoid system enhances memory formation and helps link lived experiences with specific behavioural outcomes.
In the amygdala, the emotional processing centre of the brain, certain 'gate keeper' interneurons have special receptors for endocannabinoids, and help constrain the size of the engram and the specificity of the memory.
But, when too many endocannabinoids are released, the function of the gatekeeping interneurons is disrupted, causing an increase in the size of the engram.
"Endocannabinoid receptors function like a velvet rope at an exclusive club.
When stress induces the release of too many endocannabinoids, the velvet rope falls, causing more generalised aversive fearful memories to form," explains Josselyn. r>. r>. "By blocking these endocannabinoid receptors just on these specific interneurons, we could essentially prevent one of the most debilitating symptoms of PTSD."
In 2023, previous research in Science identified larger, more generalised memory engrams in the developing brain than in the adult brain, just like stress-induced memory engrams.
As they continue to explore this unexpected link between engram size, stress and age, the teams are also delving into how daily stressors may impact happy memories.
"The many biological functions and processes that make up the complexity of human memory are still being uncovered," says Frankland, who holds a Canada Research Chair in Cognitive Neurobiology.
"We hope that as we better understand human memory, we can inform real-world therapies for those with various psychiatric and other brain disorders throughout their lifespan."
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