AMY-MPFC-EXTINCTION

Functional connectivity between the primate amygdala and the medial prefrontal cortex: role in extinction of emotional memories

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 Obiettivo del progetto (Objective)

'The purpose of this study is to bridge over an important gap between rodent and human studies. Studies in rodents have shown the importance of the reciprocal connections between the medial-prefrontal cortex (mPFC) and the amygdala, and described their contribution to the acquisition and extinction of fear-associations. In parallel, imaging studies in humans have observed activation in the mPFC-amygdala pathway during regulation of emotion, and behavioral studies in patients have revealed that dysfunction of the network underlies different psychiatric disorders. Indeed, relevant disorders are different forms of failures to regulate emotion, mainly different forms of anxiety disorders, such as PTSD. The amygdala-mPFC network is much more complex in primates than in rodents and expanded during evolution. Moreover, elaborate paradigms that mimic real-world scenarios can not be tested with rodents. Similarly, imaging studies in humans have several limitations. For example, differentiating sub-nuclei within the amygdala (and mPFC) is limited by the spatial resolution; observing complex interactions between areas during the task is limited by the low temporal resolution; and many physiological manipulations are impossible in humans. We will first record simultaneously from the amygdala and mPFC of awake- behaving monkeys during rest, electrical stimulation, and temporary inactivation of one of the structures; then, we will record during acquisition and recall of extinction of fear-associations. Our main goal is to characterize interactions between the mPFC and the amygdala, different sub-nuclei within the amygdala, and different sub-areas of the mPFC. This project will help bring the research in primates to a baseline closer to that in rodents, and will therefore validate (or not), and expand on established findings with relevance to clinical applications. Importantly, the next step of this project will study more complex forms of extinction.'

Introduzione (Teaser)

Researchers analysed the neural circuitry behind anxiety disorders.

Descrizione progetto (Article)

Fear associated behaviours such as avoidance and aggression are useful in the mammal world to cope with various threats from the environment. Acquisition of fear must be followed by its extinction in humans to avoid development of anxiety disorders such as post-traumatic stress disorder (PTSD).

Rodent studies demonstrated the importance of reciprocal connections between the medial-prefrontal cortex (mPFC) and the amygdala in relation to the acquisition and extinction of fear-associations. However, the amygdala-mPFC network is much more complex in primates than in rodents.

The EU-funded AMY-MPFC-EXTINCTION project developed a primate model for emotional learning, using tone-odour conditioning where the subjects associate pleasant and unpleasant odours with different tonal sounds.

The scientists recorded electrical stimulation from the amygdala and mPFC of awake, behaving monkeys and humans during rest. After temporary inactivation of one of the brain structures, they recorded the level of stimulation during acquisition, recall and extinction of the fear.

Using this data, AMY-MPFC-EXTINCTION tracked the neural codes that underlie learning of positive and negative memories, extinction of negative memories and failure to eliminate them. Of great significance, the researchers showed they could directly manipulate the cortex-amygdala neural pathway to prevent recovery of unpleasant memories.

Knowledge of mechanisms behind the pathways responsible for negative emotional learning and memory may provide the means to further manipulate neural information transfer. Prevention of return of aversive memories could lead to the development of therapy for anxiety disorders such as PTSD.