AMY-MPFC-EXTINCTION · Functional connectivity between the primate amygdala and the medial prefrontal cortex: role in extinction of emotional memories

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.