Extrasynaptic and synaptic NMDA receptors form stable and uniform pools in rat hippocampal slices.
N-methyl-d-aspartate receptor (NMDAR) activation can trigger both long- and short-term plasticity, promote cell survival, and initiate cell death. A number of studies suggest that the consequences of NMDAR activation can vary widely depending on whether synaptic or extrasynaptic receptors are activated. Here we have examined the spatial distribution of NMDARs of CA1 pyramidal neurons in acutely dissected hippocampal slices. Using a physiological definition of extrasynaptic receptors as those not accessible to single release events, we find that extrasynaptic NMDARs comprise a substantial proportion of the dendritic NMDAR pool (36%). This pool of extrasynaptic NMDARs is stable and does not shuttle into the synaptic receptor pool, as we observe no recovery of synaptic current after MK-801 synaptic blockade and washout. The subunit composition of synaptic and extrasynaptic NMDA receptor pools is similar at 3 weeks of age, with NR2B subunits present in both compartments. NR2B receptors are not enriched in the extrasynaptic compartment. Our data suggest that any role played by extrasynaptic NMDARs in synaptic transmission is dictated by their subcellular location rather than their subunit composition or mobility.
Harris
Alexander Z
AZ
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Ave, K426, Bronx, NY 10461, USA.
Pettit
Diana L
DL
D000818:Animals; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D010782:Photolysis; D021381:Protein Transport; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
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