The role of prediction error and memory destabilization in extinction of cued-fear within the reconsolidation window
Open accessAbstract
Extinction of a cued-fear memory within the reconsolidation window has been proposed to prevent fear reacquisition by reconsolidation interference. This 'retrieval-extinction' procedure has received interest for its therapeutic potential to reduce the impact of fear memories on behavior. To fully exploit its therapeutic potential, it is critical to understand the mechanisms that underlie the 'retrieval-extinction' effect. If the effect depends upon reconsolidation of the original memory, then it would be predicted that destabilization, induced by prediction error, would be critical for observing the effect. Here, the dependency of the retrieval-extinction effect on memory destabilization or prediction error was investigated in pavlovian cued-fear conditioned adult male rats. The requirement for memory destabilization, and thus reconsolidation, for the retrieval-extinction effect was subsequently investigated using region-specific pharmacological blockade of dopamine D1-receptors. Intra-basolateral amygdala antagonism of dopamine D1-receptors did not prevent the reacquisition of fear associated with the retrieval-extinction procedure. The requirement for prediction error was assessed by using a reinforced or non-reinforced memory retrieval trial before extinction, compared to a no-retrieval, extinction-only control. Both the reinforced (no prediction error) and non-reinforced retrieval sessions led to a decrease in fear reacquisition, suggesting that engagement of prediction error does not influence the occurrence of retrieval-extinction. Together, these data suggest that retrieval-extinction does not require memory destabilization, since behavioral or pharmacological interventions that prevent destabilization did not disrupt any capacity to attenuate fear.
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GluN2B-selective NMDAR antagonists given 1 h before extinction training do not block acquisition of the extinction memory.
“though not 1 h before training (Cahill et al., 2019)”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Cahill et al., 2019
The Materials and methods (Intracranial drug infusions and Behavioral procedures; page not specified) say drugs were infused immediately before reactivation and extinction training occurred one hour later. The Results (Antagonism of intra-BLA D1R signaling; page not specified) identify ifenprodil as a GluN2B antagonist, but report its effect on fear reacquisition, not whether it blocked acquisition of extinction memory. The reported extinction outcomes concern the D1R antagonist, so they cannot establish that outcome for ifenprodil. (LLM, conf=0.77)
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- Authors
- Cahill, E. N., Wood, M. A., Everitt, B. J., & Milton, A. L.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Cahill, Emma N.
- Venue
- Neuropsychopharmacology
- Published
- 2018-12-20
- Volume
- 44
- Issue
- 10
- Pages
- 1762-1768
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6699995
- OpenAlex
- W2904921863
- Cited by
- 40
- References
- 31
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 3
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuropsychopharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- RCUK | Biotechnology and Biological Sciences Research Council (BB/M01407X/1)
- RCUK | Medical Research Council (G1002231)
- Overseas Research Scholarship
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- fear extinction, memory reconsolidation, prediction error, memory destabilization, dopamine D1 receptor, basolateral amygdala, fear conditioning, memory retrieval, extinction therapy
- MeSH terms
- Animals, Conditioning, Classical, Cues, Extinction, Psychological, Fear, Male, Memory, Mental Recall, Reinforcement, Psychology, Receptors, Dopamine D1, Rats, Basolateral Nuclear Complex
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