(© pathdoc - stock.adobe.com)
TORONTO — Feeling frazzled lately? It turns out that stress doesn’t just impact your mood, it can fundamentally change how your brain processes and stores your memories. For people dealing with PTSD, those changes in memory can be truly debilitating.
Researchers at The Hospital for Sick Children in Toronto have made a breakthrough in understanding the inner workings of this phenomenon. By studying the brains of mice, they found that stress causes the release of endocannabinoids — chemicals that normally help us form specific, contextual memories. However, in high amounts, these endocannabinoids disrupt the brain’s “gatekeeper” neurons, leading to the formation of overly large, generalized memory engrams.
Simply put, a stressful experience doesn’t just get stored as one distinct memory. Instead, it triggers a cascade of related memories, causing people to react fearfully to all sorts of otherwise harmless triggers – such as fireworks erupting or a car backfiring.
“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,” explains Dr. Sheena Josselyn, a senior scientist at SickKids, in a media release.
Crucially, the study published in the journal Cell found a potential solution. By blocking the endocannabinoid receptors on those gatekeeper neurons, they were able to limit the stress-induced expansion of memory engrams in mice. This may lead to a promising new avenue for treating the hypervigilance and intrusive memories that plague people with PTSD.
“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,” says Josselyn in a media release.
Of course, this research was conducted in animals, not humans, so it’ll be a while before any clinical applications emerge. However, the findings shed crucial light on the complex, often counterintuitive ways that stress shapes our recollections.
In fact, the researchers also noted some surprising links between stress, memory, and the developing brain. Previous work has found that young brains tend to form larger, more generalized memory engrams compared to adult brains. Sound familiar?
“The many biological functions and processes that make up the complexity of human memory are still being uncovered,” says Dr. Paul Frankland, another senior scientist on the team.
As they continue to explore these connections, the hope is that it will inform better treatments — not just for PTSD, but a whole range of psychiatric and neurological conditions. So, if you find yourself feeling on edge these days, take comfort in the knowledge that your brain is just trying to protect you, in its own scrambled way. The good news is, there may be a way to help it get back on track.
Paper Summary
Methodology
This study investigated how stress affects memory in mice, focusing on how threatening memories become overgeneralized. Researchers trained mice to associate a specific sound with a mild foot shock. Some mice were exposed to acute stress or given a stress hormone (corticosterone) before this training. The researchers then used advanced imaging and genetic techniques to examine changes in specific brain areas, particularly the lateral amygdala, which is critical for memory and emotional responses.
By tagging active neurons during memory formation and retrieval, they tracked which brain cells were involved in specific versus generalized memories. They also manipulated certain brain signaling pathways to understand how stress influences memory precision.
Key Results
The study found that stressed mice or those given the stress hormone corticosterone had trouble distinguishing between safe and unsafe situations. Their brains activated more neurons than usual, causing them to associate non-threatening stimuli with danger. This overactivation happened because stress disrupted certain calming signals in the brain, particularly those from inhibitory neurons. When researchers blocked these disruptions, the mice regained the ability to tell safe from unsafe situations.
Study Limitations
This research focused on acute stress and its effects on threat memory in mice. It’s unclear if these findings apply to humans or to chronic stress, which develops over time. Also, the study only examined negative memories, so we don’t know if stress affects positive memories in the same way. Finally, the study used invasive methods not feasible for human studies.
Discussion & Takeaways
The study suggests that stress changes the way our brain encodes and retrieves memories, causing us to overgeneralize threats. This might explain why people with anxiety or PTSD often feel unsafe in harmless situations. The findings highlight potential treatments, like targeting specific brain pathways, to improve memory precision under stress.
Funding & Disclosures
This research was supported 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, Alzheimer Nederland, Toronto Cannabis and Cannabinoid Research Consortium, and Brain Canada Foundation.
The authors disclosed no financial conflicts of interest or affiliations that could influence the study outcomes. However, they acknowledge the role of funding sources in providing resources and infrastructure but assert that these organizations did not influence the study design, data collection, interpretation, or publication.
