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Cellular and molecular mechanisms of remote fear attenuation

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Retraining memories may help us overcome trauma

New research indicates that the best way to treat disorders associated with long-lasting fear and trauma is to reassociate the fear with a sense of safety.

Fundamental Research
Health

Traumatic events create some of our most persistent memories. Although remembering to fear these events is an important survival mechanism, when the threatening situation no longer exists, such misplaced fear can lead to anxiety and stress-related disorders. “Unfortunately, because the science of long-lasting fear remains poorly understood, we lack an effective method for treating the associated disorders,” says Johannes Gräff, a researcher with the Brain Mind Institute at the Federal Institute of Technology Lausanne, Switzerland. “This is particularly true for disorders that relate to a trauma that occurred in the distant past, such as post-traumatic stress disorder, or PTSD.” With the support of the EU-funded Remote memory traces project, Gräff is leading an effort to help fill this knowledge gap. “Our goal is to answer the big unknown questions about fear and long-lasting trauma,” adds Gräff. “In doing so, we aim to better understand how this fear can be reduced, or even eliminated.”

Face your fears

This project, supported by the European Research Council, focused its efforts on identifying the cellular populations that cause long-lasting traumatic memories to go away. To do this, researchers used mice and a unique visualisation method that let them tag any neurons that were activated by a distant memory. This in turn allowed them to identify the neuronal subpopulations that helped reduce remote memories. According to Gräff, this work demonstrated that the key to reducing long-lasting traumatic memories lies in the very same cells that were used to store the memory in the first place. “With this in mind, we believe that therapies and treatment should aim to reassociate the fear with safety and not attempt to suppress the fear itself,” explains Gräff. “In other words, the best medicine is to face your fears head-on.”

Opening the door to more effective therapies

The Remote memory traces project succeeded in developing a proof of principle according to which successful memory reduction is defined by a unique molecular signature. “We now have a tool to further investigate these cells at the molecular level, which will open the door to developing more effective therapies for treating long-lasting traumatic memories,” concludes Gräff. The project has published its findings in ‘Science’ magazine and is currently applying for additional funding.

Keywords

Remote memory traces, fear, trauma, anxiety, PTSD

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