Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor epsilon 1 or epsilon 2 subunit.
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.
Ito
I
I
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
Futai
K
K
Katagiri
H
H
Watanabe
M
M
Sakimura
K
K
Mishina
M
M
Sugiyama
H
H
D000818:Animals; D002678:Chimera; D004594:Electrophysiology; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains / Q000502:physiology*; D016296:Mutagenesis / Q000502:physiology; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013569:Synapses / Q000737:chemistry* / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate