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

• Published in: The Journal of physiology 1988-05, Vol.399 (1), p.283-300
• Main Authors: Collingridge, G L, Herron, C E, Lester, R A
• Format: Article
• Language: English
• Subjects: 2-Amino-5-phosphonovalerate; Action Potentials - drug effects; Animals; Biological and medical sciences; Central nervous system; Electrophysiology; Female; Fundamental and applied biological sciences. Psychology; Hippocampus - drug effects; Hippocampus - physiology; In Vitro Techniques; Magnesium - physiology; Neural Pathways - physiology; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter - physiology; Synapses - drug effects; Synapses - physiology; Valine - analogs & derivatives; Valine - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1988.sp017080

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 regio