Dissociating the neurobiology of fear-reducing techniques.

Anxiety disorders pose an important problem to health care and society. Experimental models propose different mechanisms to reduce fear. First, extinction learning results in the gradual decay of fearful responding due to repeated exposure to the feared stimulus. Unfortunately, extinction is not unlearning of fear but leaves the original fear memory intact. While extinction is a well-known and commonly applied technique, research is now starting to unravel an alternative method of fear reduction: reconsolidation disruption. Ground-breaking discoveries have been made in the last decade, first in animal and later in human neuroscience research, showing that upon fear re-exposure, memory can regain a sensitive, plastic state. Consequently, pharmacological manipulation of the re-stabilization process of the memory (reconsolidation) leads to long-term and more permanent fear amnesia. Thus, in contrast to extinction learning, reconsolidation allows us to directly target the fear memory. Critically, both extinction learning and reconsolidation are induced by re-exposure, but the mechanisms that dissociate the two fundamentally different processes are not yet identified. The central aim of this proposal is to reveal the neurobiological mechanisms that determine whether re-exposure engages extinction or reconsolidation mechanisms.