ABSTRACT OF THESIS FURTHERING PHARMACOLOGICAL AND PHYSIOLOGICAL ASSESSMENT OF THE GLUTAMATERGIC RECEPTORS AT THE DROSOPHILA NEUROMUSCULAR JUNCTION Drosophila larval neuromuscular junctions (NMJs) serve as a model for synaptic physiology. The molecular sequence of the postsynaptic glutamate receptors

OF THESIS FURTHERING PHARMACOLOGICAL AND PHYSIOLOGICAL ASSESSMENT OF THE GLUTAMATERGIC RECEPTORS AT THE DROSOPHILA NEUROMUSCULAR JUNCTION Drosophila larval neuromuscular junctions (NMJs) serve as a model for synaptic physiology. The molecular sequence of the postsynaptic glutamate receptors has been described; however, the pharmacological profile has not been fully elucidated. Despite the postsynaptic molecular sequence used to classify the receptors as a kainate subtype, they do not respond pharmacologically as such. Kainate does not depolarize the muscle, but dampens evoked EPSP amplitudes. Quantal responses show a decreased amplitude and area under the voltage curve indicative of reduced postsynaptic receptor sensitivity to glutamate transmission. ATPA, a kainate receptor agonist, did not mimic kainate’s action. The metabotropic glutamate receptor agonist t-ACPD had no effect. Domoic acid, a quisqualate receptor antagonist, blocks the postsynaptic receptors without depolarizing the muscle, which supports the presence of quisqualate subtype receptors. The results suggest a direct postsynaptic action of kainate due to partial antagonist action on the quisqualate receptors. There does not appear to be presynaptic auto-regulation via a kainate receptor subtype or a metabotropic auto-receptor. A complete pharmacological profiling of the known receptor subtypes at this NMJ has not yet occurred; however, this study aids in furthering the ongoing investigations to provide a clearer picture of pharmokinetic profile and specificity of the receptor subtypes.