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Inducible and Reversible NR1 Knockout Reveals Crucial Role of the NMDA Receptor in Preserving Remote Memories in the Brain
Open accessAbstract
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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“Studies using inducible and reversible NMDA receptor knockouts have demonstrated that such NMDA receptor reactivation, which may also in part result from spontaneous neuronal activity, is required to sustain remote memory storage73,74.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [73]
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Metadata
- Authors
- Cui, Z., Wang, H., Tan, Y., Zaia, K. A., Zhang, S., & Tsien, J. Z.
- Affiliations
- Princeton University (US)
- Corresponding author
- Tsien, Joe Z
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2004-03
- Volume
- 41
- Issue
- 5
- Pages
- 781-793
- ISSN
- 0896-6273 (ISSN-L)
- 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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