This project will study synaptic vesicle recycling in dopaminergic (DA) neurons. DA neurons have well-documented roles in the initiation of movement, attention and motivation, and reward-mediated learning. Deficiency or excess of DA signaling can cause devastating conditions such as Parkinson's Disease (PD) and schizophrenia respectively. DA signaling is also unique in that DA neurons exhibit tonic and phasic firing over a wide range of frequencies and durations, and that postsynaptic DA signaling occurs on slower time scales (few hundred milliseconds) than glutamate or GABA transmission (few milliseconds). While studies of neurons that release fast-acting neurotransmitters have shown that the recycling of synaptic vesicles is an important determinant of neurotransmitter release during moderate to high neuronal activity, the DA synaptic vesicle cycle has not been well studied. This project will use quantitative imaging of optical tracers to measure several parameters of synaptic vesicle recycling in DA neurons. Dopamine signaling is essential for normal neurological function and human mental health. Dopamine is contained in compartments termed synaptic vesicles, and upon activation, nerve cells release dopamine through the cycling of these vesicles. An understanding of the basic properties and molecular components of the dopamine synaptic vesicle cycle, as proposed in this study, could eventually lead to novel and more effective ways of modulating dopamine levels that could alleviate the burden of devastating conditions such as Parkinson's Disease or schizophrenia.
