Synaptic activation of N‐methyl‐D‐aspartate receptors in the Schaffer collateral‐commissural pathway of rat hippocampus.

Abstract

1. The involvement of N‐methyl‐D‐aspartate (NMDA) receptors in the response to single‐shock (0.033 Hz) stimulation of the Schaffer collateral‐commissural pathway in hippocampal slices has been investigated using current‐ and voltage‐clamp techniques. 2. In the presence of Mg2+ (1 or 2 mM) at membrane potentials near rest, the selective NMDA antagonist D‐2‐amino‐5‐phosphonovalerate (APV) had no effect on the excitatory postsynaptic potential (EPSP) and the biphasic inhibitory postsynaptic potential (IPSP) evoked by Schaffer collateral‐commissural stimulation. The recurrent IPSP evoked by antidromic stimulation of alvear fibres was also unaffected by APV. 3. The introduction of a Mg2+‐free perfusate led, at high stimulus intensity, to an orthodromically evoked epileptiform discharge but little change in the recurrent IPSP. APV suppressed a large proportion of the enhanced response in Mg2+‐free perfusate. 4. EPSPs and excitatory postsynaptic currents (EPSCs) evoked in Mg2+‐free perfusate invariably had both APV‐resistant and APV‐sensitive components. Both synaptic components had similar thresholds and latencies to onset. The APV‐sensitive component had a long time to peak and long duration. 5. Under current‐clamp conditions in Mg2+‐containing medium, an APV‐sensitive component was recorded at membrane potentials of between ‐30 and ‐10 mV, but not at potentials more negative than ‐55 mV. 6. Under voltage‐clamp, but not current‐clamp, conditions in Mg2+‐containing medium, a small APV‐sensitive component was recorded at resting membrane potentials and increased with membrane depolarization. The difference between the current‐ and voltage‐clamp data is attributed to the hyperpolarizing influence of conjointly activated IPSPs. 7. In the presence of Mg2+ and picrotoxin, a dual‐component EPSC was recorded between ‐30 and +30 mV in all cells examined. The APV‐resistant and APV‐sensitive components had similar latencies to onset. They both had reversal potentials of between ‐8 and 0 mV. The APV‐sensitive component had a longer latency to peak and duration than the APV‐resistant component. 8. It is suggested that NMDA receptors can contribute a low‐threshold and long‐duration monosynaptic component of the response evoked by low‐frequency stimulation of the Schaffer collateral‐commissural pathway. However, under physiological conditions significant expression of this component is prevented by concurrently activated IPSPs which rapidly hyperpolarize neurones into a region where Mg2+ substantially blocks NMDA channels.