Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor ε1 or ε2 subunit

Isao Ito, Kensuke Futai, Hiroyuki Katagiri, Masahiko Watanabe, Kenji Sakimura, Masayoshi Mishina, Hiroyuki Sugiyama

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

1. We have explored the effects of targeted disruption of the N-methyl-D-aspartate (NMDA) receptor ε1 or ε2 subunit gene on NMDA receptor-mediated excitatory postsynaptic currents (NMDA EPSCs) and long-term potentiations (LTPs) at the two types of synapse in mouse hippocampal CA3 pyramidal neurons: those formed by the commissural/associational (C/A) and fimbrial (Fim) inputs. 2. Electrophysiological experiments were performed in hippocampal slices prepared from both wild-type and ε1- or ε2-disrupted mice using extracellular and whole-cell patch recording techniques. To assess the ε1, ε2 and ζ1 subunit expression at cellular levels, we performed non-isotopic in situ hybridization with digoxigenin-labelled cRNA probes. 3. We could record EPSCs in response to the stimulations to either of the C/A and Fim afferents from a single CA3 pyramidal neuron. The ε1, ε2 and ζ1 subunits were expressed together in individual CA3 neurons. 4. The εl subunit disruption selectively reduced NMDA EPSCs and LTP in the C/A-CA3 synapse without significantly affecting those in the Fim-CA3 synapse, whereas the ε2 subunit mutation diminished NMDA EPSCs and LTP in the Fim-CA3 synapse with no appreciable functional modifications in the C/A-CA3 synapse. 5. These results suggest that NMDA receptors with different subunit compositions function within a single CA3 pyramidal cell in a synapse-selective manner.

Original languageEnglish
Pages (from-to)401-408
Number of pages8
JournalJournal of Physiology
Volume500
Issue number2
DOIs
Publication statusPublished - Apr 15 1997

All Science Journal Classification (ASJC) codes

  • Physiology

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