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

Research output: Contribution to journalLetter

612 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

Fingerprint

N-Methyl-D-Aspartate Receptors
Neuronal Plasticity
Glutamate Receptors
Learning
D-Aspartic Acid
Long-Term Potentiation
N-Methylaspartate
Synapses
Genes
Spatial Learning

All Science Journal Classification (ASJC) codes

  • General

Cite this

Sakimura, K., Kutsuwada, T., Ito, I., Manabe, T., Takayama, C., Kushiya, E., ... 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

Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ℰ1 subunit. / Sakimura, Kenji; Kutsuwada, Tatsuya; Ito, Isao; Manabe, Toshiya; Takayama, Chitoshi; Kushiya, Etsuko; Yagi, Takeshi; Shinichi, Aizawa; Inoue, Yoshiro; Sugiyama, Hiroyuki; Mishina, Masayoshi.

In: Nature, Vol. 373, No. 6510, 12.01.1995, p. 151-155.

Research output: Contribution to journalLetter

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, vol. 373, no. 6510, pp. 151-155. https://doi.org/10.1038/373151a0
Sakimura K, Kutsuwada T, Ito I, Manabe T, Takayama C, Kushiya E et al. Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ℰ1 subunit. Nature. 1995 Jan 12;373(6510):151-155. https://doi.org/10.1038/373151a0
Sakimura, Kenji ; Kutsuwada, Tatsuya ; Ito, Isao ; Manabe, Toshiya ; Takayama, Chitoshi ; Kushiya, Etsuko ; Yagi, Takeshi ; Shinichi, Aizawa ; Inoue, Yoshiro ; Sugiyama, Hiroyuki ; Mishina, Masayoshi. / Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ℰ1 subunit. In: Nature. 1995 ; Vol. 373, No. 6510. pp. 151-155.
@article{17c7874db7c14f6cba1cf034db39ac78,
title = "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ℰ1 subunit",
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.",
author = "Kenji Sakimura and Tatsuya Kutsuwada and Isao Ito and Toshiya Manabe and Chitoshi Takayama and Etsuko Kushiya and Takeshi Yagi and Aizawa Shinichi and Yoshiro Inoue and Hiroyuki Sugiyama and Masayoshi Mishina",
year = "1995",
month = "1",
day = "12",
doi = "10.1038/373151a0",
language = "English",
volume = "373",
pages = "151--155",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6510",

}

TY - JOUR

T1 - Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ℰ1 subunit

AU - Sakimura, Kenji

AU - Kutsuwada, Tatsuya

AU - Ito, Isao

AU - Manabe, Toshiya

AU - Takayama, Chitoshi

AU - Kushiya, Etsuko

AU - Yagi, Takeshi

AU - Shinichi, Aizawa

AU - Inoue, Yoshiro

AU - Sugiyama, Hiroyuki

AU - Mishina, Masayoshi

PY - 1995/1/12

Y1 - 1995/1/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028813106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028813106&partnerID=8YFLogxK

U2 - 10.1038/373151a0

DO - 10.1038/373151a0

M3 - Letter

C2 - 7816096

AN - SCOPUS:0028813106

VL - 373

SP - 151

EP - 155

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6510

ER -