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 NM DA receptor-mediated excitatory postsynaptic currents (NMDA EPSCs) and long-term potentiations (LTPs) at the two types of synapse in mouse h ippocampal CA3 pyramidal neurons: those formed by the commissural/asso ciational (C/A) and fimbrial (Fim) inputs. 2. Electrophysiological exp eriments were performed in hippocampal slices prepared from both wild- type and epsilon 1- or epsilon 2-disrupted mice using extracellular an d whole-cell patch recording techniques. To assess the epsilon 1, epsi lon 2 and zeta 1 subunit expression at cellular levels, we performed n on-isotopic in situ hybridization with digoxigenin-labelled cRNA probe s. 3. 3. We could record EPSCs in response to the stimulations to eith er of the C/A and Fim afferents from a single CA3 pyramidal neuron. Th e epsilon 1, epsilon 2 and zeta 1 subunits were expressed together in individual CA3 neurons. 4. The epsilon 1 subunit disruption selectivel y reduced NMDA EPSCs and LTP in the C/A-CA3 synapse without significan tly affecting those in the Fim-CA3 synapse, whereas the epsilon 2 subu nit mutation diminished NMDA EPSCs and LTP in the Fim-CA3 synapse with no appreciable functional modifications in the C/A-CA3 synapse. 5. Th ese results suggest that NMDA receptors with different subunit composi tions function within a single CA3 pyramidal cell in a synapse-selecti ve manner.