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NMDA GluN2A and GluN2B receptors play separate roles in the induction of LTP and LTD in the amygdala and in the acquisition and extinction of conditioned fear
Abstract
Synaptic plasticity mediated by NMDA glutamate receptors is thought to be a primary mechanism underlying the formation of new memories. Activation of GluN2A NMDA receptor subunits may induce long-term potentiation (LTP), whereas low-frequency stimulation of GluN2B receptors induces long-term depression (LTD). In the present study, we show that blockade of GluN2A, but not GluN2B receptors with NVP-AAM077 and Ro25-6981 respectively, prevented LTP of auditory thalamic inputs to the lateral amygdala. Conversely, LTD induction in this pathway was prevented by blockade of GluN2B, but not GluN2A receptors. As this pathway plays a critical role in the acquisition, retrieval and extinction of a learned auditory-cue fear association, we next examined the effects of blockade of GluN2A and GluN2B receptors on the development and retention of a conditioned fear response. Administration of NVP-AAM077, but not Ro25-6981, prior to conditioning disrupted the expression of conditioned fear 24h later. Conversely, Ro25-6981 but not NVP-AAM077 impaired extinction of the conditioned fear response. These data expand on previous work showing that LTP/D in the thalamic-lateral amygdala pathway is dependent on NMDA receptors, by demonstrating selective roles for GluN2A and GluN2B NMDA receptor subunits in LTP and LTD respectively. Furthermore, GluN2A receptor activation and associated LTP may be involved specifically in the initial formation and/or stabilization of a learned fear response, whereas GluN2B receptor activation and associated LTD may facilitate the suppression of Pavlovian fear responses during extinction. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
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“the acquisition of the extinction memory, but not its consolidation, is blocked by the administration of GluN2B-selective NMDAR antagonists given shortly before extinction training (Dalton et al., 2012)”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Dalton et al., 2012
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Self-citationStructure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686
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Metadata
- Authors
- Dalton, G. L., Wu, D. C., Wang, Y. T., Floresco, S. B., & Phillips, A. G.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- Floresco, Stan B.
- Phillips, Anthony G.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 62
- Issue
- 2
- Pages
- 797-806
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2089923284
- Cited by
- 144
- References
- 70
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 16 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 11 · 2016: 13 · 2015: 9 · 2014: 18 · 2013: 13 · 2012: 7
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michael Smith Health Research BC
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- NMDA receptor subunits, GluN2A, GluN2B, long-term potentiation, long-term depression, lateral amygdala, auditory fear conditioning, fear extinction, NVP-AAM077, Ro 25-6981, synaptic plasticity
- MeSH terms
- Amygdala, Animals, Association Learning, Conditioning, Classical, Extinction, Psychological, Fear, Male, Quinoxalines, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Excitatory Amino Acid Antagonists, Long-Term Synaptic Depression, Rats
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