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The ongoing projects listed below are sponsored by Vanderbilt University, National Institute on Drug Abuse, American Federation for Aging Research, and the Rosalinde and Arthur Gilbert Foundation. 1.Trafficking and recycling of synaptic vesicles Synaptic vesicles are the smallest but most essential organelle in neuron. They initiate neuronal communication at synapse by releasing signaling molecules called neurotransmitter. The behavior of synaptic vesicles has been one of the most intriguing topics in modern neurobiology. Using photoluminescent nanoparticle and 3D super-resolution microscope, we are able to follow these tiny creatures individually in live neurons. We are investigating their localization, mobility, and reuse in the context of synaptic plasticity. 2. Exo-/endocytosis in dopaminergic synapses As one of the most important neurotransmitter, dopamine has a variety of functions in brain, such as voluntary movement and reward learning. Dopamine release can be tonic and/or phasic, both of which involves the modulation of exo-/endocytosis. Implementing our single vesicle imaging in dopaminergic neurons from midbrain, we set to address the kinetics of dopamine-releasing vesicles and the regulatory mechanisms underneath. This work has great implication in drug addiction and Parkinson’s disease. 3. Vesicle retrieval and Alzheimer’s disease Soluble Amyloid-beta oligomers instead of amyloid plaques have been implicated in synaptic deconstruction and dementia in the early phase of Alzheimer’s disease. However, the underlying mechanism is unclear. We found that the retrieval of synaptic vesicles and vesicular proteins are significantly hampered in the presence of Amyloid-beta. Combining imaging and electrophysiology, we are searching for the cause and consequence of such dysfunction on synaptic transmission and plasticity.

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    Keywords

    addiction alzheimer's disease astrocyte endocytosis exocytosis homeostasis lipid membrane nanopart neuron neurotransmitter plasticity SNARE protein synapse synaptic vesicle synaptotagmin