Role of the glycine site of the N-methyl-D-aspartate receptor in synaptic plasticity induced by pairing.
In the hippocampal CA1 region of the rat, activity-dependent plasticity requires substantial postsynaptic depolarization and activation of the N-methyl-D-aspartate glutamate receptor subtype (NMDAR). Exogenous and endogenous compounds selectively modulate NMDAR function by acting at the glycine coagonist site. Here we investigate the modulatory role of the glycine site in the induction of bidirectional synaptic plasticity. Plasticity was induced by pairing low-frequency afferent pulses with different levels of postsynaptic depolarization in the absence and presence of glycine site compounds. We found strong dependence of glycine site agonist modulation on membrane voltage during induction. Thus, D-serine and glycine were more effective in enhancing long-term potentiation (LTP) during pairing of small depolarization (-60 or -50 mV) with subthreshold EPSCs than during pairing of stronger depolarization (-40 mV) with suprathreshold synaptic responses. The glycine site role in bidirectional synaptic plasticity was studied with the selective antagonist 7-chlorokynurenic acid. Blockade of the glycine site during the pairing reversed the direction of plasticity from LTP towards long-term depression. The magnitude of depression was dependent on antagonist concentration and the level of depolarization during the pairing. Thus, these experiments demonstrate the role of the glycine site in the induction of bidirectional synaptic plasticity.
Krasteniakov
N V
NV
Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, ON, K1Y 4E9, Canada.
Martina
M
M
Bergeron
R
R
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D017774:Long-Term Potentiation; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000502:physiology; D012694:Serine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D005998:Glycine