Frequency-dependent N-methyl-D-aspartate receptor-mediated synaptic transmission in rat hippocampus

• Published in: The Journal of physiology 1988-05, Vol.399 (1), p.301-312
• 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; Central neurotransmission. Neuromudulation. Pathways and receptors; Female; Fundamental and applied biological sciences. Psychology; hippocampus; Hippocampus - drug effects; Hippocampus - physiology; In Vitro Techniques; N-methyl-D-aspartic acid; Neural Pathways - physiology; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter - physiology; Synapses - drug effects; Synapses - physiology; synaptic transmission; Valine - analogs & derivatives; Valine - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1988.sp017081

1. The effects of the N-methyl-D-aspartate (NMDA) antagonist, D-2-amino-5-phosphonovalerate (APV) were examined on synaptic responses evoked by high-frequency stimulation of the Schaffer collateral-commissural pathway, in the presence of Mg2+ (1 or 2 mM) and functional synaptic inhibition. 2. The synaptic response evoked by 100 Hz stimulation comprised fast excitatory postsynaptic potentials (EPSPs) evoked by each shock and a slow depolarization. APV reduced the size of the depolarization without depressing the fast EPSPs. 3. The mean (+/- 1 S.E.) amplitude of the APV-sensitive component (3.0 +/- 0.3 mV), evoked by 100 Hz stimulation at membrane potentials near rest, was invariably smaller than the first fast EPSP (9.8 +/- 0.7 mV). Both of these synaptic components had similar thresholds and increased in amplitude as the stimulus intensity was raised. There was a positive correlation between the amplitude of the two components (r = 0.57, P less than 0.01). 4. The amplitude of the APV-sensitive component was positively correlated (r = 0.97, P less than 0.05) with the frequency of stimulation during the trains (between 10 and 100 Hz). The threshold frequency for evoking an APV-sensitive component was approximately 10 Hz. 5. In contrast to the fast EPSPs the amplitude of the APV-sensitive component increased with depolarization, and decreased with hyperpolarization, of a neurone from its resting membrane potential. The component was no longer present in some cells which had been hyperpolarized sufficiently. 6. It is suggested that during high-frequency stimulation a neurone may become depolarized for a sufficient time to reduce the Mg2+ block of NMDA channels. This enables the NMDA receptor system to contribute transiently to the synaptic response, despite the inhibitory synaptic mechanisms which prevent its activation during single-shock stimulation. The characteristics of the NMDA receptor-mediated synaptic response may explain properties relating to the induction of long-term potentiation (LTP).