DISTRIBUTION AND DEVELOPMENT OF NMDA RECEPTOR ACTIVITIES AT HIPPOCAMPAL SYNAPSES EXAMINED USING MICE LACKING THE EPSILON-1 SUBUNIT GENE

The effects of targeted disruption of the gene encoding N-methyl-D-asp artate (NMDA) receptor epsilon 1 subunit were examined in hippocampal CA1 pyramidal cell synapses and compared with the effects in the CA3 r egion. The mutation resulted in the significant reduction of NMDA rece ptor activities at the synapses in the CA1 stratum oriens, as had been observed in the CA1 stratum radiatum which we reported before. This r esult was in sharp contrast to our previous observation that in the CA 3 region, the El mutation suppressed NMDA receptors at the synapses in the stratum radiatum but not in the stratum oriens. It is suggested t hat the subunit composition of NMDA receptors may not be determined si mply by the location within a pyramidal cell, but by other factors suc h as properties of synaptic inputs. We also examined the postnatal dev elopment of long-term potentiation (LTP) in the CA3 region. The develo pment of LTP at the CA3 stratum radiatum synapses closely followed the development of the epsilon 1 subunit, and the epsilon 1 mutation stro ngly suppressed this LTP, suggesting that the targeted disruption of t he epsilon 1 subunit may not be compensated by other epsilon subunits. The LTP at the CA3 stratum oriens synapses was not significantly affe cted by the mutation at any age. (C) 1998 Elsevier Science Ireland Ltd . All rights reserved.