Fast NMDA receptor-mediated synaptic currents in neurons from mice lacking the ε2 (NR2B) subunit

Kenneth R. Tovar, Kathleen Sprouffske, Gary L. Westbrook

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

The N-methyl-D-aspartate (NMDA) receptor has been implicated in the formation of synaptic connections. To investigate the role of the ε2 (NR2B) NMDA receptor subunit, which is prominently expressed during early development, we used neurons from mice lacking this subunit. Although ε2(-/- ) mice die soon after birth, we examined whether NMDA receptor targeting to the postsynaptic membrane was dependent on the ε2 subunit by rescuing hippocampal neurons from these mice and studying them in autaptic cultures. In voltage-clamp recordings, excitatory postsynaptic currents (EPSCs) from ε2(-/-) neurons expressed an NMDA receptor-mediated EPSC that was apparent as soon as synaptic activity developed. However, compared with wild-type neurons, NMDA receptor-mediated EPSC deactivation kinetics were much faster and were less sensitive to glycine, but were blocked by Mg2+ or AP5. Whole cell currents from ε2(-/-) neurons were also more sensitive to block by low concentrations of Zn2+ and much less sensitive to the ε2-specific antagonist ifenprodil than wild-type currents. The rapid NMDA receptor- mediated EPSC deactivation kinetics and the pharmacological profile from ε2(-/-) neurons are consistent with the expression of ζ1/ε1 diheteromeric receptors in excitatory hippocampal neurons from mice lacking the ε2 subunit. Thus ε1 can substitute for the ε2 subunit at synapses and ε2 is not required for targeting of NMDA receptors to the postsynaptic membrane.

Original languageEnglish (US)
Pages (from-to)616-620
Number of pages5
JournalJournal of neurophysiology
Volume83
Issue number1
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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