Characterization of an N-methyl-D-aspartate receptor component of synaptic transmission in rat hippocampal slices.

The involvement of N-methyl-D-aspartate receptors in synaptic transmission from Schaffer collateral-commissural fibres to CA1 neurons has been investigated in rat hippocampal slices. When the perfusion medium was changed from one containing 1 mM Mg2+ to one with no added Mg2+ there was a pronounced increase in the amplitude of the population spike, the appearance of secondary population spikes and in some slices spontaneous epileptiform discharges developed. The secondary and spontaneous population spikes were abolished by the selective N-methyl-D-aspartate antagonist, D-2-amino-5-phosphonovalerate. The effects on the primary population spike depended on the strength of synaptic activation. At low intensities, the N-methyl-D-aspartate antagonist reduced or abolished this response whereas at high intensities the primary population spike was slightly increased in amplitude by this compound. Mg2+ had dose-dependent (20-500 microM) effects on synaptic responses which were identical to those of D-2-amino-5-phosphonovalerate. Increasing the Ca2+ concentration over a range of 1-3 mM also reduced or abolished secondary population spikes and, at low stimulus intensities, the primary population spike. At higher stimulus intensities, however, the primary population spike was insensitive to the Ca2+ concentration over this range. These results demonstrate the major extent to which N-methyl-D-aspartate receptors can contribute to synaptic transmission and epileptiform activity in the CA1 region of the hippocampus. They also show that an important role of Mg2+ in this region is to prevent significant activation of this receptor system during low-frequency synaptic transmission.