The Impact of Stress on Our Memories

Overgeneralized Threat MemoriesOvergeneralized threat memories occur when we associate a threatening stimulus with other stimuli that are harmless. This confusion between what is dangerous and what is not is a hallmark of psychiatric disorders such as post-traumatic stress disorder (PTSD) and generalized anxiety disorder (GAD). For instance, someone who experienced a traumatic event involving a doctor might begin to fear not only all doctors but also other figures indirectly associated with that experience, such as nurses, lawyers, or health insurance providers.

How Does Stress Affect the Memory of Negative Events? A recent study published in Cell provides new evidence on how stress alters threat memories at the neuronal level. In the study, researchers examined the formation of engrams—specific groups of neurons that store memories—in mice exposed to threatening cues. They compared a group of animals subjected to prior stress with a non-stressed group and found that stress increased engram density in the lateral amygdala, a key region for fear processing.

This heightened density was due to the inclusion of a larger number of neurons in the engram, resulting in an overgeneralization of threats. The researchers identified that parvalbumin-positive (PV+) neurons, which are responsible for maintaining engram dispersion, are modulated by stress through endocannabinoids and glucocorticoids, disrupting their function.

Promisingly, the scientists were able to reverse these effects by blocking glucocorticoid receptors or inhibiting endocannabinoid synthesis, thereby restoring normal engram dispersion. These findings pave the way for potential therapies to treat stress-related disorders such as PTSD.

Reference: Lesuis et al., Stress disrupts engram ensembles in lateral amygdala to generalize threat memory in mice, Cell (2025). DOI:10.1016/j.cell.2024.10.034