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The role of prediction error and memory destabilization in extinction of cued-fear within the reconsolidation window.
Neuropsychopharmacology. 2019 09; 44(10):1762-1768.N

Abstract

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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Authors+Show Affiliations

Cahill EN
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK. enc22@cam.ac.uk. Behavioural and Clinical Neuroscience Institute, Cambridge, CB2 3EB, UK. enc22@cam.ac.uk.
Wood MA
Behavioural and Clinical Neuroscience Institute, Cambridge, CB2 3EB, UK. Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.
Everitt BJ
Behavioural and Clinical Neuroscience Institute, Cambridge, CB2 3EB, UK. Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.
Milton AL
Behavioural and Clinical Neuroscience Institute, Cambridge, CB2 3EB, UK. Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.

MeSH

AnimalsBasolateral Nuclear ComplexConditioning, ClassicalCuesExtinction, PsychologicalFearMaleMemoryMental RecallRatsReceptors, Dopamine D1Reinforcement, Psychology

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30659275

Citation

Cahill, Emma N., et al. "The Role of Prediction Error and Memory Destabilization in Extinction of Cued-fear Within the Reconsolidation Window." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 44, no. 10, 2019, pp. 1762-1768.
Cahill EN, Wood MA, Everitt BJ, et al. The role of prediction error and memory destabilization in extinction of cued-fear within the reconsolidation window. Neuropsychopharmacology. 2019;44(10):1762-1768.
Cahill, E. N., Wood, M. A., Everitt, B. J., & Milton, A. L. (2019). The role of prediction error and memory destabilization in extinction of cued-fear within the reconsolidation window. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 44(10), 1762-1768. https://doi.org/10.1038/s41386-018-0299-y
Cahill EN, et al. The Role of Prediction Error and Memory Destabilization in Extinction of Cued-fear Within the Reconsolidation Window. Neuropsychopharmacology. 2019;44(10):1762-1768. PubMed PMID: 30659275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of prediction error and memory destabilization in extinction of cued-fear within the reconsolidation window. AU - Cahill,Emma N, AU - Wood,Melissa A, AU - Everitt,Barry J, AU - Milton,Amy L, Y1 - 2018/12/20/ PY - 2018/08/01/received PY - 2018/12/03/accepted PY - 2018/11/29/revised PY - 2019/1/20/pubmed PY - 2020/3/17/medline PY - 2019/1/20/entrez SP - 1762 EP - 1768 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 44 IS - 10 N2 - 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. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/30659275/The_role_of_prediction_error_and_memory_destabilization_in_extinction_of_cued_fear_within_the_reconsolidation_window_ DB - PRIME DP - Unbound Medicine ER -