Hippocampal Synaptic Plasticity in Mice Overexpressing an Embryonic Subunit of the NMDA Receptor
- Shigeo Okabe1,
- Carlos Collin1,
- Jonathan M. Auerbach1,
- Noam Meiri2,
- Johan Bengzon1,
- Mary B. Kennedy3,
- Menahem Segal4, and
- Ronald D. G. McKay1
- 1Laboratory of Molecular Biology and
- 2Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892,
- 3Division of Biology, California Institute of Technology, Pasadena, California 91125, and
- 4Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel
Abstract
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.
- Received January 20, 1998.
- Revision received March 9, 1998.
- Accepted March 13, 1998.
- Copyright © 1998 Society for Neuroscience
