Okabe, S., Laboratory of Molecular Biology, Natl. Inst. Neurol. Disord./Stroke, National Institutes of Health, Bethesda, MD 20892, United States, Natl. Inst. Biosci./Hum. Technology, Tsukuba, Ibaraki 305, Japan
Collin, C., Laboratory of Molecular Biology, Natl. Inst. Neurol. Disord./Stroke, National Institutes of Health, Bethesda, MD 20892, United States
Auerbach, J.M., Laboratory of Molecular Biology, Natl. Inst. Neurol. Disord./Stroke, National Institutes of Health, Bethesda, MD 20892, United States
Meiri, N., Laboratory of Adaptive Systems, Natl. Inst. Neurol. Disord./Stroke, National Institutes of Health, Bethesda, MD 20892, United States
Bengzon, J., Laboratory of Molecular Biology, Natl. Inst. Neurol. Disord./Stroke, National Institutes of Health, Bethesda, MD 20892, United States, Restorative Neurology Unit, University Hospital, Lund S-22185, Sweden
Kennedy, M.B., Division of Biology, California Institute of Technology, Pasadena, CA 91125, United States
Segal, M., Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
McKay, R.D.G., Laboratory of Molecular Biology, Natl. Inst. Neurol. Disord./Stroke, National Institutes of Health, Bethesda, MD 20892, United States, National Institutes of Health, Natl. Inst. Neurol. Dis./Stroke, Laboratory of Molecular Biology, Convent Drive-MSC 4092, Be thesda, MD 20892-4092, United States

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 Ca2+-independent activity of Ca2+- 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.