Age-dependent reduction of hippocampal LTP in mice lacking N-methyl-D-aspartate receptor ε1 subunit

The effects of targeted disruption of the N-methyl-D-aspartate (NMDA) receptor ε1 subunit gene were studied during the postnatal development of ε1-disrupted mutant mice. Using the mice at the ages of 2-3, 5-6 and 9-10 weeks, we examined NMDA receptor channel-mediated synaptic currents and long-term potentiation (LTP) in CA1 pyramidal neurons of hippocampal slices. NMDA receptor channel currents, expressed as the ratios to non-NMDA receptor channel currents, decreased with the age in both wild-type and mutant mice, but the values in the mutant mice were approximately half of those of the wild-type mice at all ages examined. The LTP in the mutant mice was also reduced, but in contrast to the NMDA receptor channel currents, the extent of the reduction in the LTP was age-dependent. The reduction was marginal at the age of 2-3 weeks, and became progressively prominent to adulthood, with the potentiation being 26% of that of the wild-type mice at 9-10 weeks.