Consolidation of extinction learning involves transfer from NMDA-independent to NMDA-dependent memory
Open accessAbstract
Extinction of conditioned fear to a tone paired with foot shock is thought to involve the formation of new memory. In support of this, previous studies have shown that extinction of conditioned fear depends on NMDA receptor-mediated plasticity. To further investigate the role of NMDA receptors in extinction, we examined the effects of the NMDA antagonist d(−)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) on the extinction of conditioned freezing and suppression of bar pressing (conditioned emotional response). Rats extinguished normally during a 90 min session in the presence of systemic CPP (10 mg/kg), but were unable to recall extinction learning 24 hr later. This suggests that an NMDA-independent form of plasticity supports short-term extinction memory, but NMDA receptors are required for consolidation processes leading to long-term extinction memory. Surprisingly, extinction learned in the presence of CPP was recalled normally when tested 48 hr after training, suggesting a delayed consolidation process that was able to improve memory in the absence of further training. Delayed consolidation involves NMDA receptors because CPP injected on the rest day between training and test prevented 48 hr recall of extinction learned under CPP. Control experiments showed that the effect of CPP on memory consolidation was not caused by state-dependent learning or reduced expression of freezing under CPP. These findings demonstrate that NMDA receptor activation is critical for consolidation of extinction learning and that this process can be initiated after training has taken place. We suggest that consolidation of extinction involves off-line relearning that reinforces extinction memory through NMDA-mediated plasticity, perhaps in prefrontal–amygdala circuits.
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Consolidation of extinction learning involves a transfer from NMDAR-independent early plasticity to NMDAR-dependent stabilisation that requires protein synthesis.
“consolidation of extinction learning involves a transfer from NMDAR-independent early plasticity to NMDAR-dependent stabilisation that requires protein synthesis.”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Santini et al., 2001
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“This finding highlights the distinct nature of neural and molecular mechanisms underlying acquisition, consolidation and retrieval of extinction memory (Santini et al. 2001).”
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- Authors
- Santini, E., Muller, R. U., & Quirk, G. J.
- Affiliations
- Ponce Health Sciences University (PR)
- State University of New York (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-11-15
- Volume
- 21
- Issue
- 22
- Pages
- 9009-9017
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762277
- OpenAlex
- W2098235001
- Cited by
- 358
- References
- 9
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 11 · 2018: 11 · 2017: 15 · 2016: 12 · 2015: 14 · 2014: 18 · 2013: 19 · 2012: 23
- FWCI
- 9.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (submittedVersion)
- Funders
- National Institutes of Health (5r01ns037150-04, 5s06gm008239-23)
- Medical Research Council
- National Institute of Mental Health (R29-MH58883, R29MH058883)
- National Institute of General Medical Sciences (S06 GM-08239, S06-GM 008239)
- National Institute of Neurological Disorders and Stroke (R01-NS37150, R01NS020686, R01 NS20686)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- extinction learning, memory consolidation, NMDA receptor, fear conditioning, conditioned freezing, conditioned emotional response, synaptic plasticity
- MeSH terms
- Amygdala, Animals, Behavior, Animal, Conditioning, Classical, Conditioning, Operant, Extinction, Psychological, Fear, Hippocampus, Learning, Male, Memory, Neuronal Plasticity, Piperazines, Mental Recall, N-Methylaspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Excitatory Amino Acid Antagonists, Rats
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