Assistant Professor of Pharmacology
410A, Robinson Research bldg Dept. Pharma., VUMC 23rd Ave. S. @ Pierce Ave., Nashville, TN, 37232-6600
Research DescriptionThe 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 Parkinsonâ€™s disease.
3. Vesicle retrieval and Alzheimerâ€™s disease
Soluble Amyloid-beta oligomers instead of amyloid plaques have been implicated in synaptic deconstruction and dementia in the early phase of Alzheimerâ€™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.
- Zhang Q, Li Y, Tsien RW. The dynamic control of kiss-and-run and vesicular reuse probed with single nanoparticles. Science [print-electronic]. 2009 Mar 3/13/2009; 323(5920): 1448-53. PMID: 19213879, PMCID: PMC2696197, PII: 1167373, DOI: 10.1126/science.1167373, ISSN: 1095-9203.
- Zhang Q, Cao YQ, Tsien RW. Quantum dots provide an optical signal specific to full collapse fusion of synaptic vesicles. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2007 Nov 11/6/2007; 104(45): 17843-8. PMID: 17968015, PMCID: PMC2077028, PII: 0706906104, DOI: 10.1073/pnas.0706906104, ISSN: 0027-8424.
- Shcherbakova OG, Hurt CM, Xiang Y, Dell'Acqua ML, Zhang Q, Tsien RW, Kobilka BK. Organization of beta-adrenoceptor signaling compartments by sympathetic innervation of cardiac myocytes. J. Cell Biol. 2007 Feb 2/12/2007; 176(4): 521-33. PMID: 17296797, PMCID: PMC2063986, PII: jcb.200604167, DOI: 10.1083/jcb.200604167, ISSN: 0021-9525.
- Zhang Q, Haydon PG. Roles for gliotransmission in the nervous system. J Neural Transm (Vienna) [print-electronic]. 2005 Jan; 112(1): 121-5. PMID: 15599610, DOI: 10.1007/s00702-004-0119-x, ISSN: 0300-9564.
- Evanko DS, Zhang Q, Zorec R, Haydon PG. Defining pathways of loss and secretion of chemical messengers from astrocytes. Glia. 2004 Aug 8/15/2004; 47(3): 233-40. PMID: 15252812, DOI: 10.1002/glia.20050, ISSN: 0894-1491.
- Zhang Q, Fukuda M, Van Bockstaele E, Pascual O, Haydon PG. Synaptotagmin IV regulates glial glutamate release. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2004 Jun 6/22/2004; 101(25): 9441-6. PMID: 15197251, PMCID: PMC438995, PII: 0401960101, DOI: 10.1073/pnas.0401960101, ISSN: 0027-8424.
- Zhang Q, Pangrsic T, Kreft M, Krzan M, Li N, Sul JY, Halassa M, Van Bockstaele E, Zorec R, Haydon PG. Fusion-related release of glutamate from astrocytes. J. Biol. Chem [print-electronic]. 2004 Mar 3/26/2004; 279(13): 12724-33. PMID: 14722063, PII: M312845200, DOI: 10.1074/jbc.M312845200, ISSN: 0021-9258.