Glycine-induced changes in synaptic efficacy in hippocampal slices involve changes in AMPA receptors.
Brief applications of high glycine concentrations to hippocampal slices have been shown to produce long-lasting changes in synaptic efficacy. In the present study, we show that glycine application transiently and reversibly increases the amplitude and prolongs the duration of synaptic potentials mediated by N-methyl-D-aspartate (NMDA) receptors. The long-lasting changes in synaptic potentials mediated by AMPA receptors are correlated with changes in the binding of [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) to membranes prepared from glycine-treated slices. The changes in binding properties of AMPA receptors in adult slices are due to an increase in affinity of the agonist for the receptor. Furthermore, glycine-induced increases in [3H]AMPA binding and in synaptic potentials in adult hippocampal slices are markedly reduced in the presence of low extracellular calcium or of the phospholipase inhibitor bromophenacylbromide. Finally, glycine-induced potentiation of synaptic potentials is associated with an increased potency of the glutamate receptor antagonist, 6,7-dinitroquinoxaline (DNQX), to inhibit synaptic potentials. The results indicate that glycine-induced changes in synaptic efficacy are likely triggered by the activation of NMDA receptors and expressed by changes in the properties of AMPA receptors. As similar events underly long-term potentiation (LTP), this phenomenon might provide important clues to elucidate the molecular mechanisms involved in LTP maintenance.
Shahi
K
K
Neuroscience Program, USC, Los Angeles 90089-2520.
Baudry
M
M
D000818:Animals; D005998:Glycine / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C056723:FG 9041; D005998:Glycine