Synaptic modulation of N-methyl-D-aspartate receptor mediated responses in hippocampus.
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.
Muller
D
D
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
Lynch
G
G
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015763:2-Amino-5-phosphonovalerate