The release of neurotransmitters at chemical synapses is a process that is central to information transmission and storage within the brain. In this project, molecular genetic approaches will be used to define the functions of synapsins, a family of proteins thought to be important for neurotransmitter release. Mice deficient in the three mammalian synapsin genes will be generated by targeted gene disruption, with the expectation that removal of synapsins will impair any synaptic functions that rely upon these proteins. Synaptic transmission will be assessed by performing electrical and optical measurements on neurons from these synapsin-deficient mice. The functions of the three synapsin genes will then be assessed by transfecting them individually into synapsin-deficient neurons and then comparing the ability of each synapsin to rescue the synaptic defects observed in the mutant neurons. Using a similar technical approach, the roles of phosphorylation in regulating the function of synapsins will be assessed by transfecting synapsins with mutations that prevent phosphorylation or with mutations that mimic permanent phosphorylation. Likewise, the role of the reversible association of synapsins with the synaptic vesicle will be addressed by imaging this process in living neurons and by determining how alterations in the association of synapsins with vesicles alters neurotransmitter release properties. These experiments should clarify important aspects of the molecular basis of communication in the brain and, ultimately, will field insights into neurological and psychiatric disorders that result from defects in synaptic transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH067044-03
Application #
6910909
Study Section
Special Emphasis Panel (ZRG1-MDCN-1 (01))
Program Officer
Asanuma, Chiiko
Project Start
2003-07-23
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$308,000
Indirect Cost
Name
Duke University
Department
Biology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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