Imagine your heart racing every time you hear fireworks, not from excitement but from fear. This reaction, tied to a single traumatic memory, is a hallmark of stress-induced memory overgeneralization. New research from The Hospital for Sick Children (SickKids) sheds light on this phenomenon and offers hope for treating post-traumatic stress disorder (PTSD).
Journal: Cell, November 15, 2024, DOI: 10.1016/j.cell.2024.10.034 | Reading time: 5 minutes
Understanding Stress-Induced Memory Generalization
Dr. Sheena Josselyn and Dr. Paul Frankland, Senior Scientists in the Neurosciences & Mental Health Program at SickKids, explored how stress alters memory encoding in the brain. Their findings, published in Cell, explain why traumatic events can cause unrelated situations to trigger fear and stress. This phenomenon, known as stress-induced aversive memory generalization, is a key feature of PTSD.
“We know that people with PTSD show fearful responses to safe situations or environments,” said Josselyn, who holds a Canada Research Chair in Circuit Basis of Memory. “We have found a way to limit this fearful response to specific situations and potentially reduce the harmful effects of PTSD.”
In collaboration with Dr. Matthew Hill from the University of Calgary’s Hotchkiss Brain Institute, the team studied how stress affects memory engrams, the brain’s physical representations of memories. They discovered that stress increases the release of endocannabinoids, disrupting key interneurons that control the specificity of memory encoding.
Mechanisms Behind the Memory Shift
Using a preclinical model, the researchers induced stress before an aversive event, creating generalized fearful memories. Typically, memory engrams involve a sparse collection of neurons, but stress caused these engrams to expand significantly, making unrelated cues more likely to trigger fear.
“Endocannabinoid receptors function like a velvet rope at an exclusive club,” Josselyn explained. “When stress induces the release of too many endocannabinoids, the velvet rope falls, causing more generalized aversive fearful memories to form.”
To counteract this effect, the team blocked endocannabinoid receptors on specific interneurons. This intervention restored the engram’s usual size, reducing generalized fear. The research highlights the endocannabinoid system’s dual role in memory formation and emotional regulation.
Real-World Implications and Future Directions
The study offers a promising avenue for addressing PTSD symptoms by targeting endocannabinoid receptors. This could pave the way for therapies that enhance memory specificity without impairing the brain’s natural stress response.
Moreover, the findings link stress-induced memory generalization to natural processes in the developing brain. A 2023 study in Science showed that younger brains naturally form larger, less-specific engrams, akin to those created by stress. Understanding this connection may reveal how daily stressors influence both positive and negative memories across different life stages.
“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,” said Frankland, who holds a Canada Research Chair in Cognitive Neurobiology.
Glossary of Key Terms
- Engram: A physical trace of a memory stored in the brain.
- Endocannabinoids: Naturally occurring molecules in the brain that regulate various functions, including stress response.
- Interneurons: Neurons that act as connectors, helping regulate brain activity.
- PTSD (Post-Traumatic Stress Disorder): A mental health condition triggered by experiencing or witnessing traumatic events.
- Memory Generalization: The process by which memories extend beyond their original context, often leading to overgeneralized fear responses.
Interactive Quiz
1. What is a memory engram?
A physical representation of a memory in the brain, involving specific neurons.
2. How does stress affect memory engrams?
Stress enlarges engrams by increasing the release of endocannabinoids, leading to generalized memories.
3. What role do interneurons play in memory encoding?
Interneurons constrain the size of memory engrams, ensuring memory specificity.
4. How might this research impact PTSD treatment?
Targeting endocannabinoid receptors could help restore memory specificity and reduce generalized fear responses.
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