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PLoS One DOI:10.1371/journal.pone.0025999

A system for performing high throughput assays of synaptic function.

Publication TypeJournal Article
Year of Publication2011
AuthorsHempel, CM, Sivula, M, Levenson, JM, Rose, DM, Li, B, Sirianni, AC, Xia, E, Ryan, TA, Gerber, DJ, Cottrell, JR
JournalPLoS One
Date Published2011
KeywordsAnimals, Cells, Cultured, Drug Discovery, High-Throughput Screening Assays, Neurons, Rats, Synapses, Synaptic Vesicles, Time Factors

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.


Alternate JournalPLoS ONE
PubMed ID21998743
PubMed Central IDPMC3187845
Grant ListR01 MH085783 / MH / NIMH NIH HHS / United States
RC4 MH092889 / MH / NIMH NIH HHS / United States
1RC4MH092889-01 / MH / NIMH NIH HHS / United States