ABC-RI researcher involved in the discovery of a physiological “brake” that prevents the formation of traumatic memories

David Brito, researcher at Algarve Biomedical Center Research Institute, has just published an article in the scientific journal “Molecular Psychiatry”, in collaboration with researchers from the Central Institute of Mental Health (Germany), the University of Heidelberg (Germany), and Vrije Universiteit Amsterdam (Netherlands). The article reveals a new biological mechanism that may play a role in regulating resilience to adverse life events.

Through experiments conducted on mice, the group of researchers, consisting of David Brito and Janina Kupke, and led by Ana MM Oliveira (Central Institute of Mental Health – University of Mannheim – Germany), discovered that the formation of highly impactful traumatic memories involves a unique molecular process that is not present in the formation and consolidation of memories of lesser impactful fear.

According to the researchers, while fear memories are essential for the organism’s survival as they trigger appropriate responses that allow adaptation to the environment, exposure to traumatic experiences can lead to the formation of strong traumatic memories that contribute to the development of serious psychiatric disorders such as post-traumatic stress disorder.

As they explain, “these strong memories are characterized by disproportionate fear responses to situations unrelated to the initial traumatic event and by the inability to extinguish these fears.”

The researchers investigated the underlying biological processes that prevent the formation of traumatic memories. To do this, and using mice as a model, neuroscientists discovered that by modulating the transcription factor Npas4, a gene involved in the regulation of neuronal development and function, it was possible to produce a response so that traumatic memories became weaker, thus reducing fear responses and events.

The researchers also demonstrated that exposure to an aversive experience leads to two elevated periods of the Npas4 transcription factor, with the second period, where researchers artificially modulated the protein, proving to be crucial as it can act as a “brake” that prevents the formation of very intense traumatic memories.

The research thus highlights the fundamental role of this protein in regulating contacts and communication between neurons, showing that when it is belatedly “activated,” it leads to the presence of the neurotransmitter responsible for reducing neuronal activity, possibly regulating the intensity of traumatic memories.

According to the research team, this study is of particular importance as it “presents Npas4 as a molecular target that can be used for the development of new therapies.”

In future studies, the research team emphasizes the importance of understanding why this intrinsic protective mechanism is sometimes bypassed, leading to the formation of pathological traumatic memories. This discovery has revealed a previously unknown biological strategy that appears to prevent highly aversive fear experiences from giving rise to strong memories that could underlie the development of psychiatric conditions.

Check the scientific article at https://www.nature.com/articles/s41380-024-02454-3.