Contextual control over conditioned responding in an extinction paradigm.

Harris, Justin A.; Jones, Megan L.; Bailey, Glynis K.; Westbrook, R. Frederick

doi:10.1037/0097-7403.26.2.174

Cited by 162 publications

(181 citation statements)

References 34 publications

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“…It has been proposed that context determines the meaning of a conditioned stimulus that has been made ambiguous by an extinction experience (Bouton, 1994). This suggests that the CS is linked to the context during extinction (Harris et al, 2000). The recovery of extinguished fear responses we observed is similar to the renewal phenomenon and suggests that vmPFC may be necessary for recalling a context in which extinction occurred.…”

Section: Discussionsupporting

confidence: 65%

The Role of Ventromedial Prefrontal Cortex in the Recovery of Extinguished Fear

et al. 2000

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Conditioned fear responses to a tone paired with footshock extinguish when the tone is presented repeatedly in the absence of shock. Rather than erase the tone-shock association, extinction is thought to involve new learning accompanied by inhibition of conditioned responding. Despite much interest in extinction from a clinical perspective, little is known about the neural circuits that are involved. Although the prefrontal cortex has a well established role in the inhibition of inappropriate behaviors, previous reports have disagreed as to the role of the ventromedial prefrontal cortex (vmPFC) in extinction. We have reexamined the effects of electrolytic vmPFC lesions made before training on the acquisition, extinction, and recovery of conditioned fear responses in a 2 d experiment. On Day 1 vmPFC lesions had no effect on acquisition or extinction of conditioned freezing and suppression of bar pressing. On Day 2 sham rats recovered only 27% of their acquired freezing, whereas vmPFC-lesioned rats recovered 86%, which was indistinguishable from a control group that never received extinction. The high recovery in lesioned rats could not be attributed to decreased motivation or altered sensitivity to footshock. vmPFC lesions that spared the caudal infralimbic (IL) nucleus had no effect. Thus, the vmPFC (particularly the IL nucleus) is not necessary for expression of extinction, but it is necessary for the recall of extinction learning after a long delay. These data suggest a role of the vmPFC in consolidation of extinction learning or the recall of contexts in which extinction took place.Key words: extinction; infralimbic; prelimbic; fear conditioning; amygdala; inhibition Prefrontal cortex has long been implicated in inhibition of inappropriate responses. Lesions of medial prefrontal cortex (mPFC) cause perseverative responding in animals and humans and cause deficits in reversal tasks (for review, see Kolb, 1984;Fuster, 1997). Perseverative responding in prefrontal animals was extended to conditioned fear when it was shown that rats with mPFC lesions could acquire freezing responses to a tone paired with a footshock, but they required many more days to extinguish those responses when the tone was presented alone (Morgan et al., 1993). More recent data support the hypothesis that mPFC is involved in the inhibition of fear responses (Bremner et al., 1999;Herry et al., 1999;Morrow et al., 1999), and it has been suggested that deficits in extinction of conditioned fear may cause certain anxiety disorders (Charney and Deutch, 1996;Pitman, 1997).Many questions remain, however, concerning the role of the ventromedial prefrontal cortex (vmPFC) in extinction of fear. Following the original report by Morgan et al. (1993), Gewirtz et al. (1997 found no effect of vmPFC lesions on extinction of conditioned fear responses. To explain this discrepancy, Gewirtz et al. (1997) suggested that the prolonged extinction might have been attributable to increased acquisition in the lesioned animals, which was masked by asymptotic freezi...

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Section: Discussionsupporting

confidence: 65%

The Role of Ventromedial Prefrontal Cortex in the Recovery of Extinguished Fear

et al. 2000

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“…28,32 A similar postextinction return of fear is observed when animals are tested in a third, novel context C following acquisition in context A and extinction in context B. 32,33 The renewal effect is not due to simple context conditioning 28,34 but rather appears to reflect an occasion-setting or modulatory role of context in gating performance to the CS. 35 Thus, rather than learning that 'now the cue is no longer paired with the shock', the animal learns that 'now, in this place, the cue is no longer paired with the shock'.…”

Section: Behavioral and Theoretical Considerationsmentioning

confidence: 69%

Mechanisms of fear extinction

2006

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Excessive fear and anxiety are hallmarks of a variety of disabling anxiety disorders that affect millions of people throughout the world. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear and anxiety is attracting increasing interest in the research community. In the laboratory, fear inhibition most often is studied through a procedure in which a previously fear conditioned organism is exposed to a fear-eliciting cue in the absence of any aversive event. This procedure results in a decline in conditioned fear responses that is attributed to a process called fear extinction. Extensive empirical work by behavioral psychologists has revealed basic behavioral characteristics of extinction, and theoretical accounts have emphasized extinction as a form of inhibitory learning as opposed to an erasure of acquired fear. Guided by this work, neuroscientists have begun to dissect the neural mechanisms involved, including the regions in which extinction-related plasticity occurs and the cellular and molecular processes that are engaged. The present paper will cover behavioral, theoretical and neurobiological work, and will conclude with a discussion of clinical implications. Molecular Psychiatry (2007) 12, 120-150.

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“…The absence of these cues on the subsequent test resulted in a failure to recall the extinction memory. This failure is an example of the well-documented phenomenon of renewal, whereby the shift of context between extinction and test restores lost fear responses (Bouton and King 1983;Bouton and Ricker 1994;Harris et al 2000). There is evidence for such an effect, as rats extinguished under a benzodiazepine showed fear responses when tested in the absence of the drug, but no such responses when tested in its presence (Bouton et al 1990).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the fear responses that are inhibited when the CS is subsequently tested in the presence of these cues are restored when it is tested in their absence. For instance, fear responses are ''renewed'' when the CS is tested either outside of the context where extinction occurred (Bouton and King 1983;Bouton and Ricker 1994;Harris et al 2000) or in the absence of drug-related cues present during extinction (Bouton et al 1990); they recover ''spontaneously'' with the elapse of time, but this recovery is attenuated when the test is preceded by a cue presented during extinction (Brooks and Bouton 1993) and they are ''reinstated'' when the extinguished CS is tested either in (Bouton and Bolles 1979), or shortly after exposure to (Morris et al 2005) a dangerous context. Just as extinction leaves intact the excitatory association produced by conditioning, recent evidence also shows that reconditioning an extinguished CS leaves intact the inhibitory association produced by extinction.…”

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confidence: 99%

Systemic or intra-amygdala injection of a benzodiazepine (midazolam) impairs extinction but spares re-extinction of conditioned fear responses

Hart¹,

Harris²,

Westbrook³

2009

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Rats were subjected to one or two cycles of fear conditioning and extinction, injected with a benzodiazepine, midazolam, before the first or second extinction, and tested for long-term inhibition of fear responses (freezing). In Experiment 1, inhibition of context-conditioned fear was spared when midazolam was injected before the second extinction, but impaired when injected before the first. In Experiment 2, it was spared when midazolam was injected before the second extinction, but only if vehicle had been injected before the first: Inhibition was impaired when the drug was injected before both. In Experiment 3, inhibition of a discrete conditioned stimulus (CS A) was spared when midazolam was injected before its second extinction, but impaired when injected before extinction of CS A in rats that had undergone extinction of CS B. In Experiment 4, inhibition was spared when midazolam was injected into the basolateral amygdala before the second extinction, but impaired when injected before the first extinction of context-conditioned fear. The results show that midazolam impairs learning, but not relearning to inhibit fear responses, and are discussed in terms of state dependency, error correction, and memory retrieval, whereby the drug's anxiolytic effects on the second extinction reactivate and strengthen the original inhibitory memory.Clinical trials have established the effectiveness of cognitivebehavioral therapy for anxiety disorders such as posttraumatic stress (Harvey et al. 2003). A component of this therapy is cue exposure in which the patient, aided by the clinician, confronts trauma-related cues in the absence of overt danger. One aim of these confrontations is to reduce, even eliminate, the ability of the trauma-related cues to elicit the fear memories that are undermining the quality of the patient's life. This aim is frequently achieved. However, the psychological processes and neural mechanisms that underlie the successes of cue exposure or that are responsible for its failures are poorly understood. Therefore, there has been much interest in laboratory models of cue exposure. One model is the extinction of Pavlovian conditioned fear responses.

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Contextual control over conditioned responding in an extinction paradigm.

Cited by 162 publications

References 34 publications

The Role of Ventromedial Prefrontal Cortex in the Recovery of Extinguished Fear

The Role of Ventromedial Prefrontal Cortex in the Recovery of Extinguished Fear

Mechanisms of fear extinction

Systemic or intra-amygdala injection of a benzodiazepine (midazolam) impairs extinction but spares re-extinction of conditioned fear responses

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