The incorporation of NMDA receptors with a distinct subunit composition at nascent hippocampal synapses in vitro

Kenneth R. Tovar, Gary Westbrook

Research output: Contribution to journalArticle

629 Citations (Scopus)

Abstract

Activity-dependent synaptic rearrangements during CNS development require NMDA receptor activation. The control of NMDA receptor function by developmentally regulated subunit expression has been proposed as one mechanism for this receptor dependence. We examined the phenotype of synaptic and extrasynaptic NMDA receptors during the development of synaptic load using the NMDA receptor 2B (NR2B)-selective antagonist ifenprodil. In cultured rat hippocampal neurons when relatively few synapses had formed, the ifenprodil block of EPSCs was less than whole-cell currents, the latter of which included both synaptic and extrasynaptic receptors. At the same developmental stage, we found that extrasynaptic receptors outnumbered synaptic receptors by 3:1; thus whole-cell currents were dominated by the extrasynaptic population. We used the macroscopic kinetics of ifenprodil block to distinguish between the receptor populations. The ifenprodil kinetics of whole-cell currents from neurons before and during the development of synaptic load was comparable with that of whole-cell currents in HEK293 cells transfected with NR1 and NR2B cDNA, indicating that extrasynaptic receptors are largely NR1/NR2B heteromers. In contrast, synaptic receptors included both a highly ifenprodil-sensitive (NR1/NR2B) component as well as a second population with lower ifenprodil sensitivity; the reduced ifenprodil block of EPSCs was attributable to synaptic receptors with lower ifenprodil sensitivity rather than to the appearance of ifenprodil-insensitive (NR1/NR2A) receptors. Our data indicate that the synaptic NMDA receptor complement changes quickly after synapse formation. We suggest that synapses containing predominately NR1/NR2B heteromers represent 'immature' sites, whereas mature sites express NMDA receptors with a distinct, presumably triheteromeric, subunit composition.

Original languageEnglish (US)
Pages (from-to)4180-4188
Number of pages9
JournalJournal of Neuroscience
Volume19
Issue number10
StatePublished - May 15 1999

Fingerprint

N-Methyl-D-Aspartate Receptors
Synapses
Neurotransmitter Receptor
Population
ifenprodil
In Vitro Techniques
Neurons
HEK293 Cells
Complementary DNA
NR2B NMDA receptor
Phenotype
NR1 NMDA receptor

Keywords

  • Hippocampus
  • Ifenprodil
  • NMDA receptors
  • Patch clamp
  • Synapse formation
  • Synaptic load

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The incorporation of NMDA receptors with a distinct subunit composition at nascent hippocampal synapses in vitro. / Tovar, Kenneth R.; Westbrook, Gary.

In: Journal of Neuroscience, Vol. 19, No. 10, 15.05.1999, p. 4180-4188.

Research output: Contribution to journalArticle

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