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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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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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A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566
Emotion circuits in the brain
LeDoux, J. E. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.155 · Cited by 8,444
Self-citation
Cloned Glutamate Receptors
Hollmann, M., & Heinemann, S. F. (1994) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.17.030194.000335 · Cited by 4,056
Long-Term Potentiation--A Decade of Progress?
Malenka, R. C., & Nicoll, A. R. A. (1999) · Science · doi:10.1126/science.285.5435.1870 · Cited by 2,729
Molecular diversity of glutamate receptors and implications for brain function
Nakanishi, S. (1992) · Science · doi:10.1126/science.1329206 · Cited by 2,543
Genetic enhancement of learning and memory in mice
Tang, Y., Shimizu, E., Dubé, G., Rampon, C., Kerchner, G. A., Zhuo, M., Liu, G., & Tsien, J. Z. (1999) · Nature · doi:10.1038/43432 · Cited by 1,878
Control of memory formation through regulated expression of a CaMKII transgene
Mayford, M., Bach, M. E., Huang, Y.-Y., Wang, L., Hawkins, R. D., & Kandel, E. R. (1996) · Science · doi:10.1126/science.274.5293.1678 · Cited by 1,550
Changing subunit composition of heteromeric NMDA receptors during development of rat cortex
Sheng, M., Cummings, J., Roldan, L. A., Jan, Y. N., & Jan, L. Y. (1994) · Nature · doi:10.1038/368144a0 · Cited by 1,377
Autophosphorylation at Thr 286 of the α Calcium-Calmodulin Kinase II in LTP and Learning
Giese, K. P., Fedorov, N. B., Filipkowski, R. K., & Silva, A. J. (1998) · Science · doi:10.1126/science.279.5352.870 · Cited by 1,055
Why We Think Plasticity Underlying Pavlovian Fear Conditioning Occurs in the Basolateral Amygdala
Fanselow, M. S., & LeDoux, J. E. (1999) · Neuron · doi:10.1016/s0896-6273(00)80775-8 · Cited by 933
Self-citation
Long-term potentiation in the hippocampus involves activation of N-methyl-D-aspartate receptors
Harris, E. W., Ganong, A. H., & Cotman, C. W. (1984) · Brain Research · doi:10.1016/0006-8993(84)90275-0 · Cited by 905
Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala
Miserendino, M. J. D., Sananes, C. B., Melia, K. R., & Davis, M. (1990) · Nature · doi:10.1038/345716a0 · Cited by 824 · cited 4×
“, 2001), several studies have found a selective effect on acquisition (Miserendino et al., 1990; Gewirtz and Davis, 1997; Walker and Davis, 2000).”
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Watkins, J. C., & Olverman, H. J. (1987) · Trends in Neurosciences · doi:10.1016/0166-2236(87)90171-8 · Cited by 694
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Schafe, G. E., Atkins, C. M., Swank, M. W., Bauer, E. P., Sweatt, J. D., & LeDoux, J. E. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-21-08177.2000 · Cited by 678
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Self-citation
Neurobiology of fear responses: the role of the amygdala
Davis, M. (1997) · Journal of Neuropsychiatry · doi:10.1176/jnp.9.3.382 · Cited by 577
Autophosphorylation-dependent Targeting of Calcium/ Calmodulin-dependent Protein Kinase II by the NR2B Subunit of theN-Methyl- d-aspartate Receptor*
Strack, S., & Colbran, R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.33.20689 · Cited by 466
Long-term potentiation in the amygdala: a mechanism for emotional learning and memory
Maren, S. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01465-4 · Cited by 462
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Maren, S., Aharonov, G., Stote, D. L., & Fanselow, M. S. (1996) · Behavioral Neuroscience · doi:10.1037//0735-7044.110.6.1365 · Cited by 385
Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus
Bashir, Z. I., Alford, S. T., Davies, S. N., Randall, A. D., & Collingridge, G. L. (1991) · Nature · doi:10.1038/349156a0 · Cited by 370
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Strack, S., McNeill, R. B., & Colbran, R. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001471200 · Cited by 356
Acquisition of contextual Pavlovian fear conditioning is blocked by application of an NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid to the basolateral amygdala.
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Long-term potentiation increases tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit 2B in rat dentate gyrus in vivo.
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Self-citation
Synaptic transmission and plasticity in the amygdala
Maren, S. (1996) · Molecular Neurobiology · doi:10.1007/bf02740749 · Cited by 139
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Weisskopf, M. G., & LeDoux, J. E. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.81.2.930 · Cited by 127
Self-citation
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Chapman, P. F., & Bellavance, L. L. (1992) · Synapse · doi:10.1002/syn.890110406 · Cited by 119
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Li, X., Phillips, R. G., & LeDoux, J. E. (1995) · Experimental Brain Research · doi:10.1007/bf00242185 · Cited by 118
Self-citation
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Fendt, M. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-11-04111.2001 · Cited by 117
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Li, H., Weiss, S. R. B., Chuang, D., Post, R. M., & Rogawski, M. A. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-05-01662.1998 · Cited by 114
Cellular and subcellular localization of the 2B-subunit of the NMDA receptor in the adult rat telencephalon
Charton, J. P., Herkert, M., Becker, C., & Schröder, H. (1999) · Brain Research · doi:10.1016/s0006-8993(98)01243-8 · Cited by 96
Distribution of choline acetyltransferase (ChAT) immunoreactivity in the brain of the adult trout and tract-tracing observations on the connections of the nuclei of the isthmus
Pérez, S. E., Y��ez, J., Marín, Ó., Anad�n, R., Gonz�lez, A., & Rodríguez‐Moldes, I. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20001218)428:3 · Cited by 96
Roles of GABAA, NMDA and muscarinic receptors in induction of long-term potentiation in the medial and lateral amygdala in vitro
Watanabe, Y., Ikegaya, Y., Saito, H., & Abe, K. (1995) · Neuroscience Research · doi:10.1016/0168-0102(94)00867-f · Cited by 93
Involvement of NMDA receptors within the amygdala in short- versus long-term memory for fear conditioning as assessed with fear-potentiated startle.
Walker, D. L., & Davis, M. E. (2000) · Behavioral Neuroscience · doi:10.1037/0735-7044.114.6.1019 · Cited by 90
Long-term enhancement of EPSP and NMDA receptor-mediated synaptic transmission in the amygdala
Gean, P.-W., Chang, F., Huang, C., Lin, J.-H., & Way, L.-J. (1993) · Brain Research Bulletin · doi:10.1016/0361-9230(93)90003-t · Cited by 84
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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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