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Neurosci Biobehav Rev. 2019 Nov 16;108:218-230. doi: 10.1016/j.neubiorev.2019.11.006. [Epub ahead of print]

Know safety, no fear.

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Department of Psychological Sciences and Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, USA. Electronic address:
Department of Psychological Sciences, Kansas State University, Manhattan, KS, USA. Electronic address:
Department of Psychological Science, Program in Neuroscience and Behavior, Vassar College, Poughkeepsie, NY, USA. Electronic address:
Center for Learning and Memory and Department of Neuroscience, University of Texas at Austin, Austin, TX, USA. Electronic address:


Every day we are bombarded by stimuli that must be assessed for their potential for harm or benefit. Once a stimulus is learned to predict harm, it can elicit fear responses. Such learning can last a lifetime but is not always beneficial for an organism. For an organism to thrive in its environment, it must know when to engage in defensive, avoidance behaviors and when to engage in non-defensive, approach behaviors. Fear should be suppressed in situations that are not dangerous: when a novel, innocuous stimulus resembles a feared stimulus, when a feared stimulus no longer predicts harm, or when there is an option to avoid harm. A cardinal feature of anxiety disorders is the inability to suppress fear adaptively. In PTSD, for instance, learned fear is expressed inappropriately in safe situations and is resistant to extinction. In this review, we discuss mechanisms of suppressing fear responses during stimulus discrimination, fear extinction, and active avoidance, focusing on the well-studied tripartite circuit consisting of the amygdala, medial prefrontal cortex and hippocampus.


Amygdala; Avoidance; Cortex; Discrimination; Extinction; Fear; Generalization; Hippocampus; Safety

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