Pre- & Post-synaptic Actions of Kainate: Negative Feedback at Glutamate -ergic Nerve Terminals

Drosophila larval neuromuscular junctions (NMJs) serve as a model for various gene mutations of synaptically relevant molecules to characterize functional consequences in synaptic physiology. In addition, the molecular sequence of the glutamate receptors on the muscle fibers have been described; however, the pharmacological profile of glutamate receptor subtypes at the NMJ have not been fully elucidated. In this study, we present evidence for self regulation (i.e. negative auto-feedback) at the NMJ in Drosophila. Based on the pharmacological profile these presynaptic autoreceptors are likely a kainate subtype of glutamate receptors. Kainate does not depolarize the muscle, but evoked EPSP dampen when kainate is present and mini frequency is reduced. Quantal responses show a decreased amplitude and area under the voltage curve indicative of some reduced postsynaptic receptor sensitivity to glutamate transmission. ATPA, a kainate receptor agonist, mimics kainate action both pre- and post-synaptically. Domoic acid, a quisqualate receptor antagonist, blocks the postsynaptic receptors without depolarizing the muscle, which supports earlier findings of the muscle containing quisqualate subtype receptors. No effects are seen on the frequency of spontaneous events in low concentration of domoic acid which causes a 50% reduction in quantal amplitude. The results suggest a kainate pre-synaptic auto-inhibitory feedback on evoked release. The feedback could be partly responsible for the rapid depression with evoked high quantal release and facilitation with evoked low quantal release during repetitive stimulation. The mechanism of action within the presynaptic terminal remains to be elucidated. The mild direct postsynaptic action of kainate is likely d ue to partial antagonist action on the quisqualate receptors. Funding:NSF-IBN-0131459 (RLC), Univ. KY (JYL), Korean Army & Korea Military Academy (JYL, WYC & NTL).