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Inducible and Reversible NR1 Knockout Reveals Crucial Role of the NMDA Receptor in Preserving Remote Memories in the Brain

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Cui, Zhenzhong, Wang, Huimin, Tan, Yuansheng, Zaia, Kimberly A, Zhang, Shuqin, Tsien, Joe Z·2004·Neuron

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Abstract

Long-term storage of information is a hallmark feature of the brain, yet routine turnover of synaptic receptors appears to be intrinsically paradoxical to this capability. To investigate how the brain preserves its delicate synaptic efficacies, we generated inducible and reversible knockout mice in which the NMDA receptor can be temporarily switched off in the forebrain specifically during the storage stage. Retention of 9-month contextual and cued fear memories is severely disrupted by prolonged, but not transient, loss of the NMDA receptor that occurs 6 months after initial training and at least 2 months prior to memory retrieval. Normal learning and memory function in subsequent tasks following the 9-month retention tests suggest that the observed retention deficits did not result from recall or performance impairment. Thus, our study reveals a hitherto unrecognized role of the NMDA receptor in dynamically maintaining the long-term synaptic stability of memory storage circuits in the brain.

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Authors: Cui, Z., Wang, H., Tan, Y., Zaia, K. A., Zhang, S., & Tsien, J. Z.
Affiliations: Princeton University (US)
Corresponding author: Tsien, Joe Z
ORCID: Cui, Zhenzhong
Zhang, Shuqin
Venue: Neuron
Publisher: Elsevier BV
Published: 2004-03
Volume: 41
Issue: 5
Pages: 781-793
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/s0896-6273(04)00072-8
OpenAlex: W2120938812
Cited by: 172
References: 62
Citations by year: 2026: 2 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 15 · 2015: 7 · 2014: 8 · 2013: 17 · 2012: 3
FWCI: 7.21
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3456 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Funders: Israel National Road Safety Authority
Burroughs Wellcome Fund
East China Normal University
W. M. Keck Foundation
National Institute of Mental Health
National Institute on Aging
Arnold and Mabel Beckman Foundation
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
Keywords: NMDA receptor, NR1 subunit, long-term memory retention, fear memory, contextual fear, cued fear, memory storage, synaptic plasticity, inducible knockout mice, forebrain, memory consolidation
MeSH terms: Animals, Brain, Fear, Female, Male, Memory, Mice, Inbred CBA, Mice, Transgenic, Synapses, Receptors, N-Methyl-D-Aspartate, Mice, Knockout, Excitatory Postsynaptic Potentials, Mice

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Inducible and Reversible NR1 Knockout Reveals Crucial Role of the NMDA Receptor in Preserving Remote Memories in the Brain

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