Postsynaptic modulation of NMDA synaptic currents in rat hippocampal microcultures by paired-pulse stimulation.
1. Paired-pulse synaptic stimulation of hippocampal neurons in microcultures resulted in depression of synaptic currents mediated by both NMDA and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. However, NMDA EPSCs were more severely depressed than AMPA EPSCs. 2. Partial NMDA receptor blockade reduced paired-pulse depression of NMDA but not of AMPA synaptic currents while partial AMPA receptor blockade had no effect on paired-pulse depression of AMPA EPSCs. These results suggest that ion flux through NMDA receptors is important in paired-pulse depression of NMDA responses but has no effect on AMPA responses. 3. Low extracellular Ca2+ concentrations or positive postsynaptic holding potentials reduced paired-pulse depression of NMDA EPSCs to near that of AMPA responses. 4. Brief paired applications of exogenous glutamate to neurons produced Ca(2+)-dependent depression similar to the depression of NMDA synaptic responses and synaptic stimulation depressed responses to exogenously applied NMDA. 5. Physiological concentrations of Mg2+ prevented expression of the postsynaptic modulation of NMDA EPSCs at -70 mV, but partial relief of Mg2+ block of the NMDA channel with depolarization increased paired-pulse depression of NMDA EPSCs.
Mennerick
S
S
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.
Zorumski
C F
CF
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008274:Magnesium; D002118:Calcium