Neuropsychopharmacology Reviews

Neuropsychopharmacology (2008) 33, 56–72; doi:10.1038/sj.npp.1301555; published online 19 September 2007

Neural Mechanisms of Extinction Learning and Retrieval

Gregory J Quirk1 and Devin Mueller1

1Department of Psychiatry, University of Puerto Rico School of Medicine, San Juan, Puerto Rico

Correspondence: Dr GJ Quirk, Department of Psychiatry, University of Puerto Rico School of Medicine, PO Box 365067, San Juan 00936-5067, Puerto Rico. Tel: +1 787 999 3058; Fax: +1 787 999 3057; E-mail:

Received 15 May 2007; Revised 11 July 2007; Accepted 29 July 2007; Published online 19 September 2007.



Emotional learning is necessary for individuals to survive and prosper. Once acquired, however, emotional associations are not always expressed. Indeed, the regulation of emotional expression under varying environmental conditions is essential for mental health. The simplest form of emotional regulation is extinction, in which conditioned responding to a stimulus decreases when the reinforcer is omitted. Two decades of research on the neural mechanisms of fear conditioning have laid the groundwork for understanding extinction. In this review, we summarize recent work on the neural mechanisms of extinction learning. Like other forms of learning, extinction occurs in three phases: acquisition, consolidation, and retrieval, each of which depends on specific structures (amygdala, prefrontal cortex, hippocampus) and molecular mechanisms (receptors and signaling pathways). Pharmacological methods to facilitate consolidation and retrieval of extinction, for both aversive and appetitive conditioning, are setting the stage for novel treatments for anxiety disorders and addictions.


infralimbic cortex, amygdala, fear conditioning, glutamate receptors, bursting, PTSD



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