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.

Public Health Relevance

The vesicular monoamine neurotransmitter transporter is required for the storage of dopamine, serotonin and other amines. We are using Drosophila to study how it localizes to specific types of secretory vesicles in neurons and how changes in localization may affect behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH107390-04
Application #
9414076
Study Section
Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
Program Officer
Driscoll, Jamie
Project Start
2015-05-01
Project End
2020-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Martin, Ciara A; Myers, Katherine M; Chen, Audrey et al. (2016) Ziram, a pesticide associated with increased risk for Parkinson's disease, differentially affects the presynaptic function of aminergic and glutamatergic nerve terminals at the Drosophila neuromuscular junction. Exp Neurol 275 Pt 1:232-41
Freyberg, Zachary; Sonders, Mark S; Aguilar, Jenny I et al. (2016) Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain. Nat Commun 7:10652
Majdi, Soodabeh; Berglund, E Carina; Dunevall, Johan et al. (2015) Electrochemical Measurements of Optogenetically Stimulated Quantal Amine Release from Single Nerve Cell Varicosities in Drosophila Larvae. Angew Chem Int Ed Engl 54:13609-12
Wasserman, Sara M; Aptekar, Jacob W; Lu, Patrick et al. (2015) Olfactory neuromodulation of motion vision circuitry in Drosophila. Curr Biol 25:467-72