Ji J, Maren S. Hippocampal involvement in contextual modulation of fear extinction. Hippocampus 17: 749-758

Department of Psychology, University of Michigan, 530 Church Street, Ann Arbor, MI 48109, USA.
Hippocampus (Impact Factor: 4.16). 09/2007; 17(9):749-58. DOI: 10.1002/hipo.20331
Source: PubMed


Extinction of fear conditioning in animals is an excellent model for the study of fear inhibition in humans. Substantial evidence has shown that extinction is a new learning process that is highly context-dependent. Several recovery effects (renewal, spontaneous recovery, and reinstatement) after extinction suggest that the contextual modulation of extinction is a critical behavioral mechanism underlying fear extinction. In addition, recent studies demonstrate a critical role for hippocampus in the context control of extinction. A growing body of evidence suggests that the hippocampus not only plays a role in contextual encoding and retrieval of fear extinction memories, but also interacts with other brain structures to regulate context-specificity of fear extinction. In this article, the authors will first discuss the fundamental behavioral features of the context effects of extinction and its underlying behavioral mechanisms. In the second part, the review will focus on the brain mechanisms for the contextual control of extinction.

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    • "Finally, in the contextual fear extinction test, in which the hippocampus plays a critical role (Ji and Maren, 2007), Salm3 −/− mice showed normal fear extinction over the course of 5 days after memory acquisition (Figure 7M). Therefore, Salm3 −/− mice display unaltered hippocampus-dependent learning and memory in the tests administered in the present study. "
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    Cell Reports 08/2015; 12(10). DOI:10.1016/j.celrep.2015.08.002 · 8.36 Impact Factor
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    • "Thus, extinction learning under placebo was strongly viewpoint-specific. These results mirror previous context-dependency findings during fear acquisition and extinction (Alvarez et al., 2007; Bouton & King, 1983; Ji & Maren, 2007). However, we note that typical contextual fear learning paradigms utilize distinguishable contexts rather than more subtle changes in viewpoint within a single environment. "
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    ABSTRACT: Alcohol is frequently involved in psychological trauma and often used by individuals to reduce fear and anxiety. We examined the effects of alcohol on fear acquisition and extinction within a virtual environment. Healthy volunteers were administered alcohol (0.4 g/kg) or placebo and underwent acquisition and extinction from different viewpoints of a virtual courtyard, in which the conditioned stimulus, paired with a mild electric shock, was centrally located. Participants returned the following day to test fear recall from both viewpoints of the courtyard. Skin conductance responses were recorded as an index of conditioned fear. Successful fear acquisition under alcohol contrasted with impaired extinction learning evidenced by persistent conditioned responses (Experiment 1). Participants' impairments in extinction under alcohol correlated with impairments in remembering object-locations in the courtyard seen from one viewpoint when tested from the other viewpoint. Alcohol-induced extinction impairments were overcome by increasing the number of extinction trials (Experiment 2). However, a test of fear recall the next day showed persistent fear in the alcohol group across both viewpoints. Thus, alcohol impaired extinction rather than acquisition of fear, suggesting that extinction is more dependent than acquisition on alcohol-sensitive representations of spatial context. Overall, extinction learning under alcohol was slower, weaker and less context-specific, resulting in persistent fear at test that generalized to the extinction viewpoint. The selective effect on extinction suggests an effect of alcohol on prefrontal involvement, while the reduced context-specificity implicates the hippocampus. These findings have important implications for the use of alcohol by individuals with clinical anxiety disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Neurobiology of Learning and Memory 07/2015; 125. DOI:10.1016/j.nlm.2015.07.014 · 3.65 Impact Factor
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    • "Extinction occurs when the CS is presented repeatedly in the absence of the US (Bouton, 1993; Herry, Ferraguti, Singewald, Letzkus, Ehrlich, & Luthi, 2010). Previous studies have shown that extinction creates a new safety association rather than erasing conditioned fear (Myers & Davis, 2002; Quirk & Mueller, 2008), as evidenced by the return of fear following the passage of time (spontaneous recovery), following presentation of the US (reinstatement), or when cues were encountered outside the extinction context (renewal) (Bouton, Westbrook, Corcoran, & Maren, 2006; Ji & Maren, 2007). Therefore, fear expression depends on the competition between reactivated memory from conditioning and reactivated memory from extinction. "
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    ABSTRACT: Recent research has used context cues (odor or auditory cues) to target memories during sleep and has demonstrated that they can enhance declarative and procedural memories. However, the effects of external cues re-presented during sleep on emotional memory are still not fully understood. In the present study, we conducted a Pavlovian fear conditioning/extinction paradigm and examined the effects of re-exposure to extinction memory associated contextual tones during slow-wave sleep (SWS) and wakefulness on fear expression. The participants underwent fear conditioning on the first day, during which colored squares served as the conditioned stimulus (CS) and a mild shock served as the unconditioned stimulus (US). The next day, they underwent extinction, during which the CSs were presented without the US but accompanied by a contextual tone (pink noise). Immediately after extinction, the participants were required to take a nap or remain awake and randomly assigned to six groups. Four of the groups were separately exposed to the associated tone (i.e. SWS-Tone group and Wake-Tone group) or an irrelevant tone (controltone, CtrT) (i.e. SWS-CtrT group and Wake-CtrT group), while the other two groups were not (i.e. SWS-No Tone group and Wake-No Tone group). Subsequently, the conditioned responses to the CSs were tested to evaluate the fear expression. All of the participants included in the final analysis showed successful levels of fear conditioning and extinction. During the recall test, the fear responses were significantly higher in the SWS-Tone group than that in the SWS-No Tone group or the SWS-CtrT group, while the Wake-Tone group exhibited more attenuated fear responses than either the Wake-No Tone group or Wake-CtrT group. Otherwise, re-exposure to auditory tones during SWS did not affect sleep profiles. These results suggested that distinct conditions during which re-exposure to an extinction memory associated contextual cue contributes to differential effects on fear expression. Copyright © 2015. Published by Elsevier Inc.
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