Abstract
We describe here a novel effect of activity on the subcellular distribution of NMDA receptors in hippocampal neurons in culture. In spontaneously active neurons, NMDA receptors were clustered at a few synaptic and nonsynaptic sites. Chronic blockade of NMDA receptor activity induced a 380% increase in the number of NMDA receptor clusters and a shift to a more synaptic distribution. This effect was reversible. The distributions of the presynaptic marker synaptophysin, the AMPA-type glutamate receptor subunit GluR1, and the putative NMDA receptor clustering protein PSD-95 were not affected by blockade. Regulation of the synaptic localization of NMDA receptors by activity may define a novel mechanism by which input controls a neuron's ability to modify its synapses.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Animals
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Cells, Cultured
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Disks Large Homolog 4 Protein
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Embryo, Mammalian
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Hippocampus / cytology
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Hippocampus / physiology*
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins / biosynthesis
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Neurons / cytology
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Neurons / physiology*
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Rats
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Receptors, AMPA / biosynthesis
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Receptors, N-Methyl-D-Aspartate / analysis
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / biosynthesis*
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Synapses / drug effects
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Synapses / physiology*
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Synapses / ultrastructure
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Synaptophysin / analysis
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Synaptophysin / biosynthesis
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Tetrodotoxin / pharmacology
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Up-Regulation / drug effects
Substances
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Synaptophysin
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postsynaptic density proteins
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Tetrodotoxin
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2-Amino-5-phosphonovalerate
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glutamate receptor ionotropic, AMPA 1