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Title

Synaptic modulation of N-methyl-D-aspartate receptor mediated responses in hippocampus

Authors
Lynch, G.
Published in Synapse. 1990, vol. 5, no. 2, p. 94-103
Abstract Low magnesium medium and the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5) were used to analyze the effect of several manipulations on the component of excitatory postsynaptic potentials (EPSPs) mediated by activation of NMDA receptors in area CA1 of hippocampal slices. The D-AP5 sensitive component of synaptic responses was characterized by a marked sensitivity to changes in extracellular magnesium and calcium concentrations. In both cases the changes in D-AP5 sensitive responses were considerably larger than those in non-NMDA-dependent potentials. Similarly, frequency facilitation, which is due to a transient increase in release, was accompanied by a greater enhancement of NMDA than non-NMDA receptor-mediated components. The degree of paired-pulse facilitation observed with D-AP5 sensitive responses was magnesium-dependent between concentrations of 0.05 and 0.5 mM, an effect not seen with control potentials. Intracellular injections of hyperpolarizing current pulses differentially affected NMDA and non-NMDA receptor-mediated components. Taken together, these results indicate that changes in the amount of transmitter release may affect to a greater degree NMDA than non-NMDA receptor-mediated components of synaptic responses, probably because of the voltage-sensitive blockade by magnesium of the NMDA receptors. In contrast, induction of long-term potentiation (LTP) by high frequency stimulation produced a larger increase in non-NMDA as opposed to NMDA receptor-dependent responses, a result that does not support the idea that an increase in transmitter release is responsible for LTP.
Keywords Action Potentials/drug effectsAnimalsElectric StimulationHippocampus/drug effects/ physiologyNeuronal Plasticity/ drug effectsRatsRats, Inbred StrainsReceptors, N-Methyl-D-AspartateReceptors, Neurotransmitter/drug effects/ physiology
Stable URL http://archive-ouverte.unige.ch/unige:10110
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PMID: 1968685
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