Stress changes how we recall memories, making them seem frightening

Every organ in the human body is extraordinary, but the brain is an organ that often surpasses our understanding. It determines how we perceive the world, how we act, and how we remember.

Our brain is hard at work – day and night. Yet, the brain is more than just an information-processing center; it’s also the epicenter of our memories, emotions, stress, and fears.

Stress can lead to more than just a stiff neck or a racing heart. In extreme cases, it can influence our brain to create and retrieve memories in strange and unusual ways.

Researchers at The Hospital for Sick Children (SickKids) have made fascinating discoveries about the relationship between stress, memory, and our brains’ biological processes.

Stress and memory: Unsettling connection

Perhaps you’ve given a presentation that didn’t go as planned. The next time you’re due to present, you might feel stressed because your brain has linked this new presentation to the memory of the previous unsatisfactory experience. This is a type of stress tied to one memory.

However, stress from traumatic events, like witnessing violence or suffering from generalized anxiety disorder, can have a far-reaching impact. It can cause what is known as stress-induced aversive memory generalization.

Here, unrelated stimuli can trigger frightening memories that seemingly have no connection to the original traumatic event. This phenomenon can have severe consequences for individuals who suffer from post-traumatic stress disorder (PTSD).

Memories after stress

Dr. Sheena Josselyn and Dr. Paul Frankland, experts in the Neurosciences & Mental Health program at SickKids, have identified the biological processes that result in stress-induced aversive memory generalization.

The experts have also found a potential intervention that could help restore the specificity of memory in individuals with PTSD.

“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,” said Dr. Josselyn.

“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.”

Understanding the mechanics

In a collaborative effort with Dr. Matthew Hill from the University of Calgary Hotchkiss Brain Institute, the research team was able to limit stress-induced aversive memory generalization to the specific, appropriate memory. This was achieved by blocking endocannabinoid receptors on interneurons.

To understand this process better, the team set up a preclinical model. They exposed subjects to a small amount of stress before a distressing event.

This created a generalized fearful memory that could be triggered by unrelated safe situations, mirroring how PTSD manifests in humans.

Upon inspecting the subjects’ memory engrams (the physical representations of a memory), the research team made an interesting discovery.

Typically, engrams involve only a small number of neurons. However, the stress-induced memory engrams involved a significantly larger number of neurons.

When they examined these larger engrams more closely, the team found that stress resulted in increased endocannabinoid release in the brain, which disrupted the function of interneurons.

Formation of fearful memories

A significant bit of the puzzle lies in a previously overlooked area — the endocannabinoid system. This system plays a key role in forming memories and associating experiences with specific behavioral outcomes.

Special “gatekeeper” interneurons in the amygdala, the emotional processing center of the brain, help constrain the size of the engram and, therefore, the specificity of the memory.

When too many endocannabinoids are released, these gatekeeper interneurons cannot function properly, leading to 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 generalized aversive fearful memories to form,” explained Dr. Josselyn.

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

Stress-induced memory engrams

In 2023, previous research published in the journal Science identified larger, more generalized memory engrams in the developing brain than in the adult brain, similar to stress-induced memory engrams.

As the experts continue to explore this unexpected connection between engram size, stress, and age, they also aim to understand how daily stressors might affect positive memories.

“The many biological functions and processes that make up the complexity of human memory are still being uncovered,” said Dr. Frankland.

“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.”

Indeed, as our understanding of the human brain continues to expand, so too do our hopes for revolutionary treatments and therapies.

Through the diligent work of these researchers and others in the field, we may be able to fully unravel the mysteries of the brain, stress, and memory.

The study is published in the journal Cell.

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