Researchers have identified a new mediator responsible for altering fear memories. This discovery could contribute to the creation of new and more effective therapies for the treatment of anxiety disorders, one of the most prevalent health conditions worldwide.

Fear-related disorders significantly affect the professional and social lives of individuals suffering from conditions associated with these disorders, such as panic disorder, post-traumatic stress disorder, and various phobias. These pathologies, characterised by exaggerated or inappropriate fear and a deficit in the extinction of fear, are highly prevalent worldwide and represent considerable governmental and societal costs.

Currently, one of the therapeutic options for anxiety disorders is exposure therapy, which is based on the fear extinction mechanism. However, neither these exposure therapies nor the use of drugs such as anxiolytics and antidepressants have proven to be 100 per cent effective in treating these disorders.

Considering the relevance of this theme to mental health, a team of researchers led by Mónica Santos, from the Center for Neuroscience and Cell Biology at the University of Coimbra (CNC-UC), carried out a study using a behavioural model of fear extinction, assessing mice that successfully extinguished fear and those that failed. The inter-individual differences in the ability to extinguish fear showed a dual outcome: firstly, on setting the vulnerability to develop anxiety and fear-related disorders, and secondly, on determining the effectiveness of exposure therapy towards patients in this group of disorders.

As uncovered in the article The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity, published in January in the journal Molecular Psychiatry, the researchers were able to identify an increase in the activation of the TrkC protein in the amygdala – the brain region that controls the fear response – at the stage of fear extinction memory formation, which leads to an increase in synaptic plasticity, i.e. the ability of neurons to change the way they communicate with each other depending on the stimuli they receive.

According to Mónica Santos, “this study has validated the TrkC pathway as a potential therapeutic target for individuals with fear-related disorders”, emphasising that “combining exposure therapies with drugs that enhance synaptic plasticity may represent a more effective and lasting way of treating anxiety disorders”.

The research team intends to continue working to “identify compounds that have the ability to specifically activate the TrkC molecule and thus be used as drugs allied to exposure therapy in the treatment of patients with anxiety disorders,” reveals Mónica Santos.

With the support of the BIAL Foundation, this project involved researchers from CNC-UC, the Faculty of Medicine of the University of Coimbra, the Faculty of Science and Technology of the University of Coimbra (Portugal), and the University of the Basque Country (Spain).

Learn more about the project “85/18 – Role of NT3/TrkC in the regulation of fear” here. Watch the video about the project here.

Full bibliographic information

Published on 18/03/2024 by BIAL Foundation
About: The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity
By: Gianluca Masella, Francisca Silva, Elisa Corti, Garikoitz Azkona, Maria Francisca Madeira, Ângelo R. Tomé, Samira G. Ferreira, Rodrigo A. Cunha, Carlos B. Duarte & Mónica Santos, Molecular Psychiatry (2024), Published: 17 January 2024,
DOI: https://doi.org/10.1038/s41380-024-02412-z.