Distribution and development of NMDA receptor activities at hippocampal synapses examined using mice lacking the ε1 subunit gene

The effects of targeted disruption of the gene encoding N-methyl-D-aspartate (NMDA) receptor ε1 subunit were examined in hippocampal CA1 pyramidal cell synapses and compared with the effects in the CA3 region. The mutation resulted in the significant reduction of NMDA receptor activities at the synapses in the CA1 stratum oriens, as had been observed in the CA1 stratum radiatum which we reported before. This result was in sharp contrast to our previous observation that in the CA3 region, the ε1 mutation suppressed NMDA receptors at the synapses in the stratum radiatum but not in the stratum oriens. It is suggested that the subunit composition of NMDA receptors may not be determined simply by the location within a pyramidal cell, but by other factors such as properties of synaptic inputs. We also examined the postnatal development of long-term potentiation (LTP) in the CA3 region. The development of LTP at the CA3 stratum radiatum synapses closely followed the development of the ε1 subunit, and the ε1 mutation strongly suppressed this LTP, suggesting that the targeted disruption of the ε1 subunit may not be compensated by other ε subunits. The LTP at the CA3 stratum oriens synapses was not significantly affected by the mutation at any age.