GLYCINE-INDUCED CHANGES IN SYNAPTIC EFFICACY IN HIPPOCAMPAL SLICES INVOLVE CHANGES IN AMPA RECEPTORS

Brief applications of high glycine concentrations to hippocampal slice s have been shown to produce long-lasting changes in synaptic efficacy . In the present study, we show that glycine application transiently a nd reversibly increases the amplitude and prolongs the duration of syn aptic potentials mediated by N-methyl-D-aspartate (NMDA) receptors. Th e long-lasting changes in synaptic potentials mediated by AMPA recepto rs are correlated with changes in the binding of pha-amino-3-hydroxy-5 -methylisoxazole-4-proprionic acid ([H-3]AMPA) to membranes prepared f rom glycine-treated slices. The changes in binding properties of AMPA receptors in adult slices are due to an increase in affinity of the ag onist for the receptor. Furthermore, glycine-induced increases in [H-3 ]AMPA binding and in synaptic potentials in adult hippocampal slices a re markedly reduced in the presence of low extracellular calcium or of the phospholipase inhibitor bromophenacylbromide. Finally, glycine-in duced potentiation of synaptic potentials is associated with an increa sed potency of the glutamate receptor antagonist, 6,7-dinitroquinoxali ne (DNQX), to inhibit synaptic potentials. The results indicate that g lycine-induced changes in synaptic efficacy are likely triggered by th e activation of NMDA receptors and expressed by changes in the propert ies of AMPA receptors. As similar events underly long-term potentiatio n (LTP), this phenomenon might provide important clues to elucidate th e molecular mechanisms involved in LTP maintenance.