The Influence of Neurotransmitter Transport on Aminergic Neuromodulation



 DESCRIPTION (provided by applicant): Vesicular monoamine transporters (VMATs) are required for the storage and exocytotic release of all aminergic neurotransmitters. The mechanisms by which VMATs target to secretory vesicles remain unclear and the potential behavioral consequences of disrupting their localization are unknown. We are using the model organism Drosophila melanogaster to address these questions. The mutations we have generated thus far decrease the localization of Drosophila VMAT (DVMAT) to Synaptic Vesicles (SVs) and increase its localization to Large Dense Core Vesicles (LDCVs). The behavioral sequelae of these mutations provide some of the first information on the function of amine release from SVs versus LDCVs. We will now generate additional mutations to decrease the localization of DVMAT to LDCVs. These mutants will be useful for further behavioral tests and also help to define fundamental trafficking mechanisms in neurons. Additional experiments will use these mutants to define the poorly understood differences between trafficking in aminergic versus non-aminergic neurons and to determine how changes in amine release affect pre- and post-synaptic function in aminergic circuits. Further behavioral experiments will explore the affects of altered amine release in more complex behaviors and the response to aminergic drugs. The results of these experiments will be significant because they examine processes relevant to conserved neuromodulatory processes and the clinical effects of aminergic drugs. They are innovative because they exploit several new assays and because no other lab has examined the in vivo effects of mis-trafficking for a vesicular transporter, or the behavioral effects of changing the way neurotransmitters are released from particular vesicle types.