Our group studies how the brain overcomes fear, by focusing on extinction of Pavlovian fear conditioning. In fear extinction, an individual learns that a stimulus that once predicted danger no longer does. This simple form of learning generates a memory of safety that competes with memories of fear to control behavior. It is thought that deficits in extinction learning underlie anxiety disorders (such as phobias and PTSD) as well as addictions. We use a number of techniques in systems neuroscience to study the neural mechanisms of extinction, including: lesions, microinfusion, multichannel unit recording, brain stimulation, and immunocytochemistry. In collaboration with other groups (some in PR), we have employed patch clamp recording, cDNA microarrays, computational modeling, and human brain imaging. We have identified structures in the prefrontal cortex that inhibit the output of the amygdala, thereby reducing expression of fear memories following extinction. We are currently studying the cellular and molecular mechanism of prefrontal plasticity in extinction, with the long-term goal of facilitating extinction for clinical benefit. Our work is funded by the NIMH and NIGMS.