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Stress responses and threat processing are central to understanding debilitating disorders such as Anxiety and Posttraumatic stress disorder (PTSD). Recent progress has been made in understanding the neural circuits underlying threat-or fear-memory formation that complements a decades-old appreciation of the neurobiology of fear, involving hub structures such as the amygdala. I will review evidence from our lab and others for genetic, neurobiological, and neural circuit mechanisms that underlie fear processing in preclinical neuroscience model systems, and how these findings can be used to help understand Posttraumatic Stress Disorder (PTSD) and other trauma-related disorders in human patients. I will also discuss future approaches to pharmacotherapy and other treatments for PTSD that have been developed via bench to bedside translational models.