Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor epsilon 1 or epsilon 2 subunit

J Physiol. 1997 Apr 15;500 ( Pt 2)(Pt 2):401-8. doi: 10.1113/jphysiol.1997.sp022030.


1. We have explored the effects of targeted disruption of the N-methyl-D-aspartate (NMDA) receptor epsilon 1 or epsilon 2 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 epsilon 1- or epsilon 2-disrupted mice using extracellular and whole-cell patch recording techniques. To assess the epsilon 1, epsilon 2 and zeta 1 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 epsilon 1, epsilon 2 and zeta 1 subunits were expressed together in individual CA3 neurons. 4. The epsilon 1 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 epsilon 2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chimera
  • Electrophysiology
  • Hippocampus / chemistry
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Long-Term Potentiation / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Inbred ICR
  • Mice, Mutant Strains / physiology*
  • Mutagenesis / physiology
  • Organ Culture Techniques
  • Pyramidal Cells / chemistry
  • Pyramidal Cells / physiology
  • Pyramidal Cells / ultrastructure
  • Receptors, N-Methyl-D-Aspartate / chemistry
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / chemistry*
  • Synapses / physiology


  • Receptors, N-Methyl-D-Aspartate