TY - JOUR T1 - Hippocampal Synaptic Plasticity in Mice Overexpressing an Embryonic Subunit of the NMDA Receptor JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4177 LP - 4188 DO - 10.1523/JNEUROSCI.18-11-04177.1998 VL - 18 IS - 11 AU - Shigeo Okabe AU - Carlos Collin AU - Jonathan M. Auerbach AU - Noam Meiri AU - Johan Bengzon AU - Mary B. Kennedy AU - Menahem Segal AU - Ronald D. G. McKay Y1 - 1998/06/01 UR - http://www.jneurosci.org/content/18/11/4177.abstract N2 - 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. ER -