Generating new neurons to circumvent your fears: the role of IGF signaling.

Extinction of fear memory is a particular form of cognitive function that is of special interest because of its involvement in the treatment of anxiety and mood disorders. Based on recent literature and our previous findings (EMBO J 30(19):4071-4083, 2011), we propose a new hypothesis that implies a tight relationship among IGF signaling, adult hippocampal neurogenesis and fear extinction. Our proposed model suggests that fear extinction-induced IGF2/IGFBP7 signaling promotes the survival of neurons at 2-4 weeks old that would participate in the discrimination between the original fear memory trace and the new safety memory generated during fear extinction. This is also called "pattern separation", or the ability to distinguish similar but different cues (e.g., context). To understand the molecular mechanisms underlying fear extinction is therefore of great clinical importance.