REDUCED HIPPOCAMPAL LTP AND SPATIAL-LEARNING IN MICE LACKING NMDA RECEPTOR EPSILON-1 SUBUNIT

THE NMDA (N-methyl-D-aspartate) receptor channel is important for syna ptic plasticity, which is thought to underlie learning, memory and dev elopment(1,2). The NMDA receptor channel is formed by at least two mem bers of the glutamate receptor (GluR) channel subunit families, the Gl uR epsilon (NR2) and GluR zeta (NR1) subunit families(3-8). The four e psilon subunits are distinct in distribution, properties and regulatio n(5-14). On the basis of the Mg2+ sensitivity and expression patterns, we have proposed that the epsilon 1 (NR2A) and epsilon 2 (NR2B) subun its play a role in synaptic plasticity(6,14). Here we show that target ed disruption of the mouse epsilon 1 subunit gene resulted in signific ant reduction of the NMDA receptor channel current and long-term poten tiation at the hippocampal CA1 synapses. The mutant mice also showed a moderate deficiency in spatial learning. These results support the no tion that the NMDA receptor channel-dependent synaptic plasticity is t he cellular basis of certain forms of learning.