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Faculty

Eric Schwartz, MD Eric Schwartz, MD
Professor

Department of Pharmacological and Physiological Sciences
The University of Chicago
947 E. 58th St., MC0926
Chicago, IL 60637

Email: easy@uchicago.edu
Phone: (773) 702-6382
Fax: (773) 834-0616
Office: SBRI J-251 (MC 0926)

 

Research Summary

Mechanisms of synaptic transmission

Research Description

In my laboratory we combine electrical, optical, and molecular biology techniques to study mechanisms of synaptic transmission.  Recently, we have investigated two topics: 1) the function of transporters that move synaptic transmitter molecules across membranes, and 2) the control of synaptic vesicle exocytosis and endocytosis.

Transporters are proteins that move transmitters in both directions across cell membranes.  In most neurons, transporters function to uptake transmitters after release.  However, in some neurons transporters also operate in the opposite direction and function in the release of transmitter.  A cell’s membrane voltage controls the balance between uptake and release.  Experiments on cloned transporters are designed to reveal the exact mechanism of how a transporter protein moves a transmitter molecule across a membrane.

The control of vesicle cycling has been studied by recording the synaptic signal transmitted between identified cells is a retinal slice.  Measurements of the post synaptic event produced by the release of a single vesicle can be compared to the total current produced during normal transmission.  The result allows us to estimate the kinetics of synaptic vesicle mobilization and cycling. 

Vesicle cycling is also being studied in solitary cells.  Measurements of cell capacitance can detect the minute change in surface area that occurs when vesicles fuse with the surface membrane.  Alternatively, vesicles can be labeled with fluorescent dyes and their movements imaged with quantitative methods. 

Currently we are developing a new system to study vesicle cycling.  Molecular biology methods have been used to introduce fluorescent proteins into zebrafish.  We have engineered fusion proteins that are expressed in synaptic vesicles.  Therefore, the movement of vesicles (with their fluorescent tags) can be observed using optical methods.  Our favorite cells are bipolar neurons in the retina and beta cells in the pancreas.  Bipolar cells have an unusually large synaptic terminal (5-10 µM diameter); and, beta cells have relatively large vesicles.  To observe the movement of vesicles in both cell types, we have constructed microscopes that combine total internal reflection (TIR), gradient imaging, and digitally-enhanced differential interference contrast (DEDIC).  These methods allow us to resolve single 30 nm vesicles in a zebrafish bipolar cell.  We expect to use TIR and correlation spectroscopy to study the mechanics of vesicle cycling and the movement of vesicle proteins in the plasmalemma.

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