a system for performing high throughput assays of synaptic function系统进行高通量检测突触功能.pdfVIP

A System for Performing High Throughput Assays of Synaptic Function 1 1 1 1 1 1 Chris M. Hempel , Michael Sivula , Jonathan M. Levenson , David M. Rose , Bing Li , Ana C. Sirianni , 1 2 1 1 Eva Xia , Timothy A. Ryan , David J. Gerber , Jeffrey R. Cottrell * 1 Galenea Corporation, Cambridge, Massachusetts, United States of America, 2 Department of Biochemistry, Weill Cornell Medical College, New York, New York, United States of America Abstract Unbiased, high-throughput screening has proven invaluable for dissecting complex biological processes. Application of this general approach to synaptic function would have a major impact on neuroscience research and drug discovery. However, existing techniques for studying synaptic physiology are labor intensive and low-throughput. Here, we describe a new high- throughput technology for performing assays of synaptic function in primary neurons cultured in microtiter plates. We show that this system can perform 96 synaptic vesicle cycling assays in parallel with high sensitivity, precision, uniformity, and reproducibility and can detect modulators of presynaptic function. By screening libraries of pharmacologically defined compounds on rat forebrain cultures, we have used this system to identify novel effects of compounds on specific aspects of presynaptic function. As a system for unbiased compound as well as genomic screening, this technology has significant applications for basic neuroscience research and for the discovery of novel, mechanism-based treatments for central nervous system disorders. Citation: Hempel CM, Sivula M, Levenson JM, Rose DM, Li B, et al. (2011)