Input-specific targeting of NMDA receptor subtypes at mouse hippocampal CA3 pyramidal neuron synapses

Isao Ito, Ryosuke Kawakami, Kenji Sakimura, Masayoshi Mishina, Hiroyuki Sugiyama

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Hippocampal CA3 pyramidal neurons receive synaptic inputs from commissural and associational fibers on both apical and basal dendrites. NMDA receptors at these synapses were examined in hippocampal slices of wild-type mice and GluRε1 (NR2A) subunit knockout mice. Electrical stimulations at the CA3 stratum radiatum or stratum oriens activate both commissural and associational (C/A) synapses, whereas stimulations at ventral fimbria mainly activate commissural synapses. Ro 25-6981 and ifenprodil, the GluRε2 (NR2B) subunit-selective NMDA receptor antagonists, suppressed NMDA receptor- mediated excitatory postsynaptic currents (NMDA EPSCs) at the commissural-CA3 synapses on basal dendrites more strongly than those at the C/A-CA3 synapses on apical or basal dendrites. However, glutamate-evoked NMDA receptor currents were reduced by the GluRε1 subunit knockout to a similar extent at both apical and basal dendrites. The GluRε1 subunit knockout also reduced NMDA EPSCs at the C/A-CA3 synapses on basal dendrites, but did not affect NMDA EPSCs at the commissural-CA3 synapses on basal dendrites. These results confirmed our previous findings that NMDA receptors operating at different synapses in CA3 pyramidal cells have different GluRε subunit compositions, and further show that the GluRε subunit composition may be regulated depending on the types of synaptic inputs, even within a single CA3 pyramidal neuron. (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)943-951
Number of pages9
JournalNeuropharmacology
Volume39
Issue number6
DOIs
Publication statusPublished - May 2000

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

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