Platelet-activating factor and group I metabotropic glutamate receptors interact for full development and maintenance of long-term potentiation in the rat medial vestibular nuclei

In rat brainstem slices, we investigated the interaction between platelet-a ctivating factor and group I metabotropic glutamate receptors in mediating long-term potentiation within the medial vestibular nuclei. We analysed the N1 field potential wave evoked in the ventral portion of the medial vestib ular nuclei by primary vestibular afferent stimulation. The group I metabot ropic glutamate receptor antagonist, (R,S)-1-aminoindan-1,5-dicarboxylic ac id, prevented long-term potentiation induced by a platelet-activating facto r analogue [1-O-hexadecyl-2-O-(methylcarbamyl)-sn-glycero-3-phosphocoline], as well as the full development of potentiation, induced by high-frequency stimulation under the blocking agent for synaptosomal platelet-activating factor receptors (ginkolide B), at drug washout. However, potentiation dire ctly induced by the group I glutamate metabotropic receptor agonist, (R,S)- 3,5-dihydroxyphenylglycine, was reduced by ginkolide B. These findings sugg est that platelet-activating factor, whether exogenous or released followin g potentiation induction, exerts its effect through presynaptic group I met abotropic glutamate receptors, mediating the increase of glutamate release. In addition, we found that this mechanism, which led to full potentiation through presynaptic group I metabotropic glutamate receptor activation, was inactivated soon after application of potentiation-inducing stimulus. In f act, the long-lasting block of the platelet-activating factor and metabotro pic glutamate receptors prevented the full potentiation development and the induced potentiation progressively declined to null. Moreover, ginkolide B , given when high-frequency-dependent potentiation was established, only re duced it within 5 min after potentiation induction. We conclude that to fully develop vestibular long-term potentiation require s presynaptic events. Platelet-activating factor, released after the activa tion of postsynaptic mechanisms which induce potentiation, is necessary for coupling postsynaptic and presynaptic phenomena, through the activation of group I metabotropic glutamate receptors, and its action lasts only for a short period. If this coupling does not occur, a full and long-lasting pote ntiation cannot develop. (C) 1999 IBRO. Published by Elsevier Science Ltd.