Inducible and reversible NR1 knockout reveals crucial role of the NMDA receptor in preserving remote memories in the brain

Zhenzhong Cui, Huimin Wang, Yuansheng Tan, Kimberly A. Zaia, Shuqin Zhang, Joseph Zhuo Tsien

Research output: Contribution to journalArticle

134 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)781-793
Number of pages13
JournalNeuron
Volume41
Issue number5
DOIs
StatePublished - Mar 4 2004

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Long-Term Memory
N-Methyl-D-Aspartate Receptors
Brain
Neurotransmitter Receptor
Information Storage and Retrieval
Prosencephalon
Knockout Mice
Fear
Learning
Retention (Psychology)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inducible and reversible NR1 knockout reveals crucial role of the NMDA receptor in preserving remote memories in the brain. / Cui, Zhenzhong; Wang, Huimin; Tan, Yuansheng; Zaia, Kimberly A.; Zhang, Shuqin; Tsien, Joseph Zhuo.

In: Neuron, Vol. 41, No. 5, 04.03.2004, p. 781-793.

Research output: Contribution to journalArticle

Cui, Zhenzhong ; Wang, Huimin ; Tan, Yuansheng ; Zaia, Kimberly A. ; Zhang, Shuqin ; Tsien, Joseph Zhuo. / Inducible and reversible NR1 knockout reveals crucial role of the NMDA receptor in preserving remote memories in the brain. In: Neuron. 2004 ; Vol. 41, No. 5. pp. 781-793.
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