title: A system for performing high throughput assays of synaptic function.
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.
authors: Galenea Corporation, Cambridge, Massachusetts, United States of America.
authors: Chris M
authors: CM
authors: Hempel
authors: Michael
authors: M
authors: Sivula
authors: Jonathan M
authors: JM
authors: Levenson
authors: David M
authors: DM
authors: Rose
authors: Bing
authors: B
authors: Li
authors: Ana C
authors: AC
authors: Sirianni
authors: Eva
authors: E
authors: Xia
authors: Timothy A
authors: TA
authors: Ryan
authors: David J
authors: DJ
authors: Gerber
authors: Jeffrey R
authors: JR
authors: Cottrell
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D055808:Drug Discovery; D057166:High-Throughput Screening Assays / Q000379:methods*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D051381:Rats; D013569:Synapses / Q000187:drug effects* / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects; D013997:Time Factors