UCLA

Drosophila neuromuscular junctions are powerful models for the investigation of synaptic and neuronal circuit function as well as the regulation of muscle contraction. We have used the well- characterized larval neuromuscular junction (NMJ) as a model to investigate the neurophysiological effects of ziram and other pesticides linked to Parkinson’s Disease. Using electrophysiology and calcium imaging, we show that ziram alters two separate aspects of neurophysiology by disrupting two distinct pathways. It causes an increase in synaptic vesicle release at least in part through disruption of the protein ubiquitination pathway. Secondly, ziram enhances excitability at both aminergic and glutamatergic neurons by blocking either directly or indirectly the eag family of potassium channels. We additionally use the adult reproductive tract NMJ to investigate the regulation of muscle contraction by the excitatory transmitter glutamate. We show that ionotropic and metabotropic glutamate receptors have a distinct pattern of expression on the reproductive tract muscle and in local neurons. Ionotropic receptors are expressed in the muscle cells and are important for the initial glutamate-induced muscle contraction. By contrast, metabotropic glutamate receptors are expressed only in local cells extrinsic to the muscle and are important for the rhythmic pattern of activity underlying muscle contraction. We suggest that cells expressing the metabotropic receptor may relay signals from neurons to the muscle and be important for modulation of muscle activity.