HIPPOCAMPAL SYNAPTIC PLASTICITY IN MICE OVEREXPRESSING AN EMBRYONIC SUBUNIT OF THE NMDA RECEPTOR

The effects of changing NMDA receptor subunit composition on synaptic plasticity in the hippocampus were analyzed by creating transgenic mic e overexpressing NR2D, a predominantly embryonic NMDA receptor subunit . NMDA-evoked currents in the transgenic mice had smaller amplitudes a nd slower kinetics, The transgenics also displayed age-dependent defic its in synaptic plasticity in area CA1 of the hippocampus. Long-term d epression was selectively impaired in juvenile mice when NR2D overexpr ession was moderate. In mature mice, overexpression of NR2D was associ ated with a reduction of both NR2B and Ca2+-independent activity of Ca 2+- and calmodulin-dependent protein kinase II. These biochemical chan ges were correlated with a marked impairment of NMDA-dependent long-te rm potentiation, but spatial behavior was normal in these mice. These results show that the developmental regulation of NMDA receptor subuni t composition alters the frequency at which modification of synaptic r esponses occur after afferent stimulation.