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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Age Factors
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Animals
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Behavior, Animal / physiology
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Calcium Channel Blockers / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Electrophysiology
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Excitatory Amino Acid Antagonists / pharmacology
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Gene Expression Regulation, Developmental / physiology*
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Hippocampus / chemistry*
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Hippocampus / physiology*
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Long-Term Potentiation / physiology
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Magnesium / pharmacology
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Maze Learning / physiology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Transgenic
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Neuronal Plasticity / physiology*
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Nifedipine / pharmacology
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Phosphorylation
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Receptors, N-Methyl-D-Aspartate / genetics*
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Spatial Behavior / physiology
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Synapses / chemistry
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Synapses / enzymology
Substances
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Calcium Channel Blockers
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Excitatory Amino Acid Antagonists
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Receptors, N-Methyl-D-Aspartate
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2-Amino-5-phosphonovalerate
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases
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Magnesium
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Nifedipine