How Difficult Events Alter Memories

Summary: Researchers have discovered how anxiety disrupts memory precision, leading to broad aversive memories—a essence of PTSD. Stress increases opioid launch, enlarging memory engrams in the mind, which triggers wary responses to related, safe situations.

In preliminary models, blocking opioid receptors on particular interneurons gave rise to desire for PTSD treatment. These findings provide new insights into the biological mechanisms that contribute to the inference of stress-induced storage and facilitate medical intervention.

Important Information:

• Stress enlarges storage engrams, creating broad fearful recollections.
• Endocannabinoid overproduction destroys cells that limit the size of engrams.
• In PTSD versions, cannabinoid receptor blockade restored recollection specificity.

Origin: Hospital for Sick Kids

Researchers at The Hospital for Sick Children ( SickKids ) have discovered that stress alters how our brains encode and retrieve aversive memories, and they have found a promising new method to restore appropriate memory specificity in those suffering from post-traumatic stress disorder ( PTSD ). &nbsp, &nbsp,

If&nbsp, you stumble&nbsp, during&nbsp, a lecture, you&nbsp, may feel stressed the next time you have to provide because your mind associates&nbsp, your&nbsp, next&nbsp, demonstration with that&nbsp, one&nbsp, poor&nbsp, and aversive&nbsp, knowledge. &nbsp, This&nbsp, form of&nbsp, strain is tied to one memory.

But pressure from&nbsp, traumatic&nbsp, events like violence&nbsp, or broad stress disorder&nbsp, is spread&nbsp, far&nbsp, beyond the initial event, known as stress-induced aversive memory generalization, where&nbsp, fireworks or car backfires&nbsp, can&nbsp, trigger&nbsp, apparently unrelated&nbsp, fearful&nbsp, memories&nbsp, and&nbsp, derail&nbsp, your entire day. In&nbsp, the circumstance of PTSD, &nbsp, it can&nbsp, produce much greater adverse effects. &nbsp, &nbsp,

In a review published in&nbsp, Cell, &nbsp, Drs. &nbsp, Sheena Josselyn&nbsp, and&nbsp, Paul Frankland, Top Scientists in the&nbsp, Neurosciences &amp, Mental Health system, identify the physiological processes behind stress-induced aversive storage generalization and highlight an intervention which may help restore suitable memory specificity for people with PTSD. &nbsp,

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

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

Together with their colleague Dr. Matthew Hill at the&nbsp, 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 the specific, appropriate memory. &nbsp,

Stress-induced memory generalization&nbsp,

In a preclinical model, the research team used an acute, but safe stress before an aversive event to create a non-specific fearful memory that could be triggered by unrelated, safe situations, similar to how PTSD manifests in people. &nbsp, &nbsp,

The team then examined the subject’s memory engrams, which are physical representations of a memory in the brain pioneered by the&nbsp, Josselyn and Frankland labs&nbsp, at SickKids.

Usually, engrams are made up of a sparse number of neurons, but the stress-induced memory engrams involved significantly more neurons. Generalized fearful memories were produced by these larger engrams, which were even recovered in secure settings. &nbsp,

The study discovered that stress increased the release of endogenous cannabinoids, which interfered with the function of interneurons, which limited the size of the engram.

Memory and the endocannabinoid system&nbsp,

The endocannabinoid system assists in the synthesis of memories and facilitates the connection between specific behavioral outcomes and lived experiences.

In the amygdala, the emotional processing centre of the brain, certain’ gate keeper ‘ interneurons have special receptors for endocannabinoids, and help &nbsp, constrain the size of the engram and the specificity of the memory. &nbsp,

But, when too many endocannabinoids are released, the function of the gatekeeping interneurons is disrupted, causing an increase in the size of the engram. &nbsp,

” At a classy club, the endocannabinoid receptors act like velvet ropes.” When stress induces the release of too many endocannabinoids, the velvet rope falls, causing more generalized aversive fearful memories to form”, explains Josselyn.

We could essentially avoid one of the most crippling PTSD symptoms by blocking these endocannabinoid receptors on these specific interneurons.

A surprising link between stress and the developing brain&nbsp, &nbsp,

In 2023, &nbsp, previous research in&nbsp, Science&nbsp, identified larger, more generalized memory engrams in the developing brain than in the adult brain, just like stress-induced memory engrams.

The teams are looking into how daily stressors may affect happy memories as they continue to explore this unanticipated link between engram size, stress, and age. &nbsp,

” The many biological functions and processes that make up the complexity of human memory are still being uncovered”, says Frankland, who&nbsp, holds a Canada Research Chair in Cognitive Neurobiology.

We hope that as we gain a better understanding of human memory, we can guide the treatment of people with a range of psychiatric and other brain disorders throughout their lives.

Funding: This research was funded by the Canadian Institutes of Health Research ( CIHR ), the Natural Sciences and Engineering Research Council of Canada ( NSERC ), the Dutch Research Council, Niels Stensen Fellowship, ZonMw Memorabel, &nbsp, Alzheimer Nederland, Toronto Cannabis and Cannabinoid Research Consortium and Brain Canada Foundation. &nbsp,

About this information on research into memory and stress

Author: Jelena Djurkic
Source: Hospital for Sick Children
Contact: Jelena Djurkic – Hospital for Sick Children
Image: The image is credited to Neuroscience News

Original Research: Open access.
Sheena Josselyn and colleagues ‘ study,” To generalize threat memory in mice, stress disrupts engram ensembles in the lateral amygdala..” Cell

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Abstract

To generalize threat memory in mice, stress disrupts engram ensembles in the lateral amygdala.

Stress induces aversive memory overgeneralization, a hallmark of many psychiatric disorders. A sparse ensemble of neurons that are active during an event ( an engram ensemble ) encodes memories.

We looked at the molecular and circuitry that control the overgeneralization of stress-induced threat memory in mice.

The density of engram ensembles supporting a threat memory in the lateral amygdala was increased by stress, which used corticosterone, to reactivate this ensemble using both specific and non-specific retrieval cues ( generalized threat memory ).

Furthermore, we identified a critical role for endocannabinoids, acting retrogradely on parvalbumin-positive ( PV+ ) lateral amygdala interneurons in the formation of a less-sparse engram and memory generalization induced by stress.

In stressed mice, glucocorticoid receptor antagonists, endocannabinoid synthesis inhibitors, and reducing cannabinoid receptors in lateral amygdala PV+ neurons caused a loss of memory specificity and a weak engram.

These findings offer insights into stress-induced memory alterations, providing potential therapeutic avenues for stress-related disorders.