Intra-Amygdala Blockade of the NR2B Subunit of the NMDA Receptor Disrupts the Acquisition But Not the Expression of Fear Conditioning

Rodrigues, Sarina M.; Schafe, Glenn E.; LeDoux, Joseph E.

doi:10.1523/jneurosci.21-17-06889.2001

Cited by 350Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Intra-Amygdala Blockade of the NR2B Subunit of the NMDA Receptor Disrupts the Acquisition But Not the Expression of Fear Conditioning

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Rodrigues, Sarina M., Schafe, Glenn E., LeDoux, Joseph E.·2001·The Journal of Neuroscience

DOI 10.1523/jneurosci.21-17-06889.2001PMC PMC6763096

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Abstract

The lateral nucleus of the amygdala (LA) is an essential component of the neural circuitry underlying Pavlovian fear conditioning. Although blockade of NMDA receptors in LA and adjacent areas before training disrupts the acquisition of fear conditioning, blockade before testing also often disrupts the expression of fear responses. With this pattern of results, it is not possible to distinguish a contribution of NMDA receptors to plasticity from a role in synaptic transmission. In past studies, NMDA blockade has been achieved using the antagonist d,l-2-amino-5-phosphovalerate, which blocks the entire heteromeric receptor complex. The present experiments examined the effects of selective blockade of the NR2B subunit of the NMDA receptor in LA using the selective antagonist ifenprodil. Systemic injections of ifenprodil before training led to a dose-dependent impairment in the acquisition of auditory and contextual fear conditioning, whereas injections before testing had no effect. Intra-amygdala infusions of ifenprodil mirrored these results and, in addition, showed that the effects are attributable to a disruption of fear learning rather than a disruption of memory consolidation. NMDA receptors in LA are thus involved in fear conditioning, and the NR2B subunit appears to make unique contributions to the underlying plasticity.

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Several lines of indirect evidence support the idea that this plasticity occurs as a result of a Hebbian mechanism through which depolarization of LA pyramidal neurons by the shock US coincident with weaker activation of the same cells by auditory CS inputs results in fear learning.
“Several lines of indirect evidence support the idea that this plasticity occurs as a result of a Hebbian mechanism through which depolarization of LA pyramidal neurons by the shock US coincident with weaker activation of the same cells by auditory CS inputs results in fear learning (8–18).”
From Optical activation of lateral amygdala pyramidal cells instructs associative fear learning (2010) · cites this paper as [15]
The NMDA receptor plays a critical role in fear extinction.
“Likewise, though the molecular mechanism of contextual fear extinction remains to be precisely determined, the N-methyl-D-aspartate (NMDA) receptor appears to play a critical role in fear extinction (Falls et al, 1992;Ledgerwood et al, 2003Ledgerwood et al, , 2004Ledgerwood et al, , 2005;;Rodrigues et al, 2001;Santini et al, 2001;Walker et al, 2002).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Rodrigues et al, 2001

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Correction
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Authors: Rodrigues, S. M., Schafe, G. E., & LeDoux, J. E.
Affiliations: W. M. Keck Foundation (US)
New York University (US)
ORCID: LeDoux, Joseph E.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2001-09-01
Volume: 21
Issue: 17
Pages: 6889-6896
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.21-17-06889.2001
PMC: PMC6763096
OpenAlex: W2108961156
Cited by: 350
References: 55
Citations by year: 2026: 4 · 2025: 8 · 2024: 9 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 9 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 14 · 2015: 15 · 2014: 19 · 2013: 23 · 2012: 16
FWCI: 8.60
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: W. M. Keck Foundation
York University
National Institute of Mental Health (MH-58911, R37MH038774, P50MH058911, R01MH046516)
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: NMDA receptor, NR2B subunit, ifenprodil, lateral amygdala, fear conditioning, fear acquisition, fear expression, memory consolidation, synaptic plasticity, auditory fear conditioning, contextual fear conditioning, NMDA receptor antagonism
MeSH terms: Acoustic Stimulation, Amygdala, Animals, Conditioning, Classical, Dose-Response Relationship, Drug, Drug Administration Schedule, Electroshock, Fear, Injections, Intraperitoneal, Learning, Male, Memory, Short-Term, Microinjections, Piperidines, Retention, Psychology, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Excitatory Amino Acid Antagonists, Rats

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Intra-Amygdala Blockade of the NR2B Subunit of the NMDA Receptor Disrupts the Acquisition But Not the Expression of Fear Conditioning

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