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

✍ Scribed by Dr. Dominique Muller; Gary Lynch


Publisher
John Wiley and Sons
Year
1990
Tongue
English
Weight
965 KB
Volume
5
Category
Article
ISSN
0887-4476

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✦ Synopsis


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) mediateed by activation of NDMA receptors in area CA1 of hippocampal slices. The D‐AP5 sensitive component of synaptic response 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 agreater 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 increases in transmitter release is responsible for LTP.


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