Stress impairs memory and causes unnecessary anxiety: here’s why

It has long been suspected that stress or having suffered some type of trauma can make you feel fear or anxiety in innocuous situations. For example, after burning a finger on a hot pan, a stressed person might avoid not only hot pans, but also the kitchen or even cooking. This type of generalized fear is common in people with post-traumatic stress disorder (PTSD) and generalized anxiety disorder.

Now, the study published in ‘Cell’ describes how stress alters the formation of memories, particularly those related to scary events. The results, they write in their conclusions, provide information on stress-induced memory impairments, offering possible therapeutic avenues for stress-related disorders, such as PTSD and anxiety.

Memories are organized into groups of neurons, called engrams, that are activated during the formation of a memory. The team of Sheena Josselynneuroscientist Hospital for Sick Children in Torontoinvestigated whether stress interferes with the formation of engrams and focused on the amygdala, a brain region linked to stress and emotions.

The study included a three-step experiment with adult mice. Firstinduced stress in some mice by injecting them with the stress hormone corticosterone or placing them in a small tube for 30 minutes, which raised their corticosterone levels.

Subsequently, they placed the mice—some stressed and others not—in a camera and they played a medium-pitch sound for 30 seconds, a neutral event. After a break, the mice returned to the chamber and heard a 30-second high-pitched sound that ended with a 2-second electric shock to the paws, simulating a fear event.

To assess how they stored memories, the researchers placed the mice in a new environment and played the two sounds, observing their reactions.

paralyzing fear

The unstressed mice primarily froze when hearing the high-pitched sound, while the stressed ones reacted to both sounds, suggesting that they could not distinguish between neutral and fearful events.

Using various techniques to visualize neuronal activity, the researchers found that unstressed mice formed small engrams associated with the whistle and the electric shock, which were reactivated only by the whistle. However, the stressed mice formed larger engrams, reactivated by both sounds.

The experiments showed that, under normal conditions, neurons in the amygdala release GABA to limit neuronal activity, forming small engrams. Under stress, endocannabinoids They inhibit the release of GABA, allowing the activation of more neurons and generating larger engrams.

“It’s like the velvet curtain in a nightclub: it only lets certain neurons in,” he explains in an article in ‘Nature‘ Josselyn.

Under stress, excitatory neurons release a neurotransmitter called endocannabinoid, which binds to glucocorticoid receptors on inhibitory neurons and prevents them from releasing GABA, generating larger engrams. In other words, the curtain falls and “many neurons can enter the exclusive club,” he adds.

The team was able to reverse the effects of stress on memory formation with two drugs, one of which, mifepristoneis approved to terminate early pregnancies. The drugs block glucocorticoid receptors or endocannabinoid production, making stressed mice remember like non-stressed ones.

However, researchers warn that these drugs have side effects and only work if administered during memory formation, limiting their usefulness in humans.

Josselyn and her colleagues are now investigating whether engrams can be modified after they are formed or whether there are other ways to mitigate the effects of stress on memory.