Implications of memory modulation for post-traumatic stress and fear disorders

Abstract

Post-traumatic stress disorder, panic disorder and phobia manifest in ways that are consistent with an uncontrollable state of fear. Their development involves heredity, previous sensitizing experiences, association of aversive events with previous neutral stimuli, and inability to inhibit or extinguish fear after it is chronic and disabling. We highlight recent progress in fear learning and memory, differential susceptibility to disorders of fear, and how these findings are being applied to the understanding, treatment and possible prevention of fear disorders. Promising advances are being translated from basic science to the clinic, including approaches to distinguish risk versus resilience before trauma exposure, methods to interfere with fear development during memory consolidation after a trauma, and techniques to inhibit fear reconsolidation and to enhance extinction of chronic fear. It is hoped that this new knowledge will translate to more successful, neuroscientifically informed and rationally designed approaches to disorders of fear regulation.

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Figure 1: Schematic depicting the amygdala, the brain site most critical for fear learning.
Figure 2: A model for the development of fear-related disorders.
Figure 3: Basic fear conditioning and testing procedures.
Figure 4: Human neural circuitry involved in fear-related disorders and PTSD.
Figure 5: Different components of fear learning and modulation as they are studied in the laboratory.

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Acknowledgements

Support was provided by the US National Institutes of Health (F32MH090700, R01MH071537, R01MH094757 and R01MH096764), the Burroughs Wellcome Fund and a US National Institutes of Health National Center for Research Resources base grant (P51RR000165) to Yerkes National Primate Research Center.

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Correspondence to Kerry J Ressler.

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K.J.R. is a cofounder of Therapade/Extinction LLC for the licensing of d-cycloserine for the enhancement of psychotherapy. K.J.R. has received no income or royalties from this relationship in the past 3 years.

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Parsons, R., Ressler, K. Implications of memory modulation for post-traumatic stress and fear disorders. Nat Neurosci 16, 146–153 (2013). https://doi.org/10.1038/nn.3296

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