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Hippocampal Synaptic Plasticity in Mice Overexpressing an Embryonic Subunit of the NMDA Receptor

Okabe, Shigeo and Collin, Carlos and Auerbach, Jonathan M. and Meiri, Noam and Bengzon, Johan and Kennedy, Mary B. and Segal, Menahem and McKay, Ronald D. G. (1998) Hippocampal Synaptic Plasticity in Mice Overexpressing an Embryonic Subunit of the NMDA Receptor. Journal of Neuroscience, 18 (11). pp. 4177-4188. ISSN 0270-6474. PMCID PMC6792823. doi:10.1523/jneurosci.18-11-04177.1998.

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The effects of changing NMDA receptor subunit composition on synaptic plasticity in the hippocampus were analyzed by creating transgenic mice overexpressing NR2D, a predominantly embryonic NMDA receptor subunit. NMDA-evoked currents in the transgenic mice had smaller amplitudes and slower kinetics. The transgenics also displayed age-dependent deficits in synaptic plasticity in area CA1 of the hippocampus. Long-term depression was selectively impaired in juvenile mice when NR2D overexpression was moderate. In mature mice, overexpression of NR2D was associated with a reduction of both NR2B and Ca^(2+)-independent activity of Ca^(2+)- and calmodulin-dependent protein kinase II. These biochemical changes were correlated with a marked impairment of NMDA-dependent long-term potentiation, but spatial behavior was normal in these mice. These results show that the developmental regulation of NMDA receptor subunit composition alters the frequency at which modification of synaptic responses occur after afferent stimulation.

Item Type:Article
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URLURL TypeDescription CentralArticle
Kennedy, Mary B.0000-0003-1369-0525
Segal, Menahem0000-0002-1828-7682
Additional Information:© 1998 Society for Neuroscience. Received Jan. 20, 1998; revised March 9, 1998; accepted March 13, 1998. J.M.A. was supported by a Human Frontier Science Program Long-Term Fellowship. We thank Drs. M. Mayford and E. R. Kandel for the CaMK promoter, Drs. P. Seeburg and M. Hollmann for NMDA receptor cDNAs, Drs. R. J. Wenthold, B. Wolfe, M. Sheng, and A. Czernik for antibodies, and Drs. C. J. McBain and M. L. Mayer for valuable comments on this manuscript.
Funding AgencyGrant Number
Human Frontier Science ProgramUNSPECIFIED
Subject Keywords:hippocampus; NMDA receptor; long-term potentiation; long-term depression; water maze; transgenic mice
Issue or Number:11
PubMed Central ID:PMC6792823
Record Number:CaltechAUTHORS:20120424-154218718
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Official Citation: Shigeo Okabe, Carlos Collin, Jonathan M. Auerbach, Noam Meiri, Johan Bengzon, Mary B. Kennedy, Menahem Segal, and Ronald D. G. McKay Hippocampal Synaptic Plasticity in Mice Overexpressing an Embryonic Subunit of the NMDA Receptor The Journal of Neuroscience, 1 June 1998, 18(11):4177-4188
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:30324
Deposited By: Melanie Stefan
Deposited On:25 Apr 2012 23:01
Last Modified:09 Nov 2021 19:45

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