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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bliss, T. V. P. & Collingridge, G. L. Nature 361, 31–39 (1993).
Morris, R. G. M., Anderson, E., Lynch, G. S. & Baudry, M. Nature 319, 774–776 (1986).
Moriyoshi, K. et al. Nature 354, 31–37 (1991).
Yamazaki, M. et al. FEBS Lett. 300, 39–45 (1992).
Meguro, H. et al. Nature 357, 70–74 (1992).
Kutsuwada, T. et al. Nature 358, 36–41 (1992).
Monyer, H. et al. Science 256, 1217–1221 (1992).
Ikeda, K. et al. FEBS Lett. 313, 34–38 (1992).
Watanabe, M., Inoue, Y., Sakimura, K. & Mishina, M. NeuroReport 3, 1138–1140 (1992).
Watanabe, M., Inoue, Y., Sakimura, K. & Mishina, M. J. comp. Neurol. 338, 337–390 (1993).
Mori, H., Yamakura, T., Masaki, H. & Mishina, M. NeuroReport 4, 519–522 (1993).
Ishii, T. et al. J. biol. Chem. 268, 2836–2843 (1993).
Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B. & Seeburg, P. H. Neuron 12, 529–540 (1994).
Mishina, M. et al. Ann. N.Y. Acad. Sci. 707, 136–152 (1993).
Yagi, T. et al. Analyt. Biochem. 214, 70–76 (1993).
Li, Y. et al. Cell 76, 427–437 (1994).
Abeliovich, A. et al. Cell 75, 1253–1262 (1993).
Morris, R. G. M. Learn. Motiv. 12, 239–260 (1981).
Silva, A. J., Stevens, C. F., Tonegawa, S. & Wang, Y. Science 257, 201–206 (1992).
Davis, S., Butcher, S. P. & Morris, R. G. M. J. Neurosci. 12, 21–34 (1992).
Silva, A. J., Paylor, R., Wehner, J. M. & Tonegawa, S. Science 257, 206–211 (1992).
Grant, S. G. N. et al. Science 258, 1903–1910 (1992).
Umemori, H., Sato, S., Yagi, T., Aizawa, S. & Yamamoto, T. Nature 367, 572–576 (1994).
Abeliovich, A. et al. Cell 75, 1263–1271 (1993).
Yagi, T. et al. Analyt. Biochem. 214, 77–86 (1993).
Araki, K. et al. Biochem. biophys. Res. Commun. 197, 1267–1276 (1993).
Ito, I. & Sugiyama, H. NeuroReport 2, 333–336 (1991).
Blanton, M. G., Lo Turco, J. J. & Kriegstein, A. R. J. Neurosci. Meth. 30, 203–210 (1989).
Coleman, P. A. & Miller, R. F. J. Neurophysiol. 61, 218–230 (1989).
Zhang, Y., Saito, H. & Nishiyama, N. Brain Res. 658, 127–134 (1994).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sakimura, K., Kutsuwada, T., Ito, I. et al. Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit. Nature 373, 151–155 (1995). https://doi.org/10.1038/373151a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/373151a0
This article is cited by
-
Allosteric inhibition of phosphodiesterase 4D induces biphasic memory-enhancing effects associated with learning-activated signaling pathways
Psychopharmacology (2024)
-
The molecular pathology of schizophrenia: an overview of existing knowledge and new directions for future research
Molecular Psychiatry (2023)
-
Loss of Grin2a causes a transient delay in the electrophysiological maturation of hippocampal parvalbumin interneurons
Communications Biology (2023)
-
GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia
Molecular Psychiatry (2023)
-
Maternal PUFAs, Placental Epigenetics, and Their Relevance to Fetal Growth and Brain Development
Reproductive Sciences (2023)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.