Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ℰ1 subunit

Kenji Sakimura, Tatsuya Kutsuwada, Isao Ito, Toshiya Manabe, Chitoshi Takayama, Etsuko Kushiya, Takeshi Yagi, Aizawa Shinichi, Yoshiro Inoue, Hiroyuki Sugiyama, Masayoshi Mishina

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634 Citations (Scopus)

Abstract

THE NMDA (TV-methyl-D-aspartate) receptor channel is important for synaptic plasticity, which is thought to underlie learning, memory and development1, 2. The NMDA receptor channel is formed by at least two members of the glutamate receptor (GluR) channel subunit families, the GluRε (NR2) and GiuRζ (NR1) sub-unit families3–8. The four ε subunits are distinct in distribution, properties and regulation5–14. On the basis of the Mg2+sensitivity and expression patterns, we have proposed that the εi (NR2A) and ε2 (NR2B) subunits play a role in synaptic plasticity6, 14. Here we show that targeted disruption of the mouse εl subunit gene resulted in significant reduction of the NMDA receptor channel current and long-term potentiation at the hippocampal CA1 synapses. The mutant mice also showed a moderate deficiency in spatial learning. These results support the notion that the NMDA receptor channel-dependent synaptic plasticity is the cellular basis of certain forms of learning.

Original languageEnglish
Pages (from-to)151-155
Number of pages5
JournalNature
Volume373
Issue number6510
DOIs
Publication statusPublished - Jan 12 1995

All Science Journal Classification (ASJC) codes

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    Sakimura, K., Kutsuwada, T., Ito, I., Manabe, T., Takayama, C., Kushiya, E., Yagi, T., Shinichi, A., Inoue, Y., Sugiyama, H., & Mishina, M. (1995). Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ℰ1 subunit. Nature, 373(6510), 151-155. https://doi.org/10.1038/373151a0