Activity regulates the synaptic localization of the NMDA receptor in hippocampal neurons.
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.
Rao
A
A
Department of Cell and Structural Biology, University of Illinois, Urbana 61801, USA.
Craig
A M
AM
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D018091:Receptors, AMPA / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D016708:Synaptophysin / Q000032:analysis / Q000096:biosynthesis; D013779:Tetrodotoxin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D015763:2-Amino-5-phosphonovalerate; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; D013779:Tetrodotoxin; C501449:Dlg4 protein, rat; C033652:postsynaptic density proteins