Activity-dependent signaling: influence on plasticity in circuits controlling fear-related behavior

•Fear regulation is impaired in anxiety and trauma-related disorders.•Patterns of neural activity and functional connectivity regulate fear and anxiety behavior.•Fear regulation is influenced by activity-dependent signaling.•BDNF is a prototypical activity-dependent molecule that is implicated in fear-related disorders.

Fear regulation is impaired in anxiety and trauma-related disorders. Patients experience heightened fear expression and reduced ability to extinguish fear memories. Because fear regulation is abnormal in these disorders and extinction recapitulates current treatment strategies, understanding the underlying mechanisms is vital for developing new treatments. This is critical because although extinction-based exposure therapy is a mainstay of treatment, relapse is common. We examine recent findings describing changes in network activity and functional connectivity within limbic circuits during fear regulation, and explore how activity-dependent signaling contributes to the neural activity patterns that control fear and anxiety. We review the role of the prototypical activity-dependent molecule, brain-derived neurotrophic factor (BDNF), whose signaling has been critically linked to regulation of fear behavior.