Discussion

One of the major challenges in phenotypic screening is to maintain relevance to the intact organism while striving to achieve a higher throughput. In studies of the central nervous system (CNS), this involves the ability to test network activity and plasticity in higher-throughput assays. Primary neuronal cell cultures are considered to be relevant in vitro models of functional activity. Neuronal viability is commonly used as the endpoint for phenotypic assays, but may not truly reflect neuronal dysfunction in neurodegenerative diseases. Rather, functional changes, such as excitability, structural changes and/or synapse strength alterations occur much earlier than cell death and thus serve as more relevant read-outs. Therefore, assays that enable identification of compounds affecting such events are highly desired. We have developed a medium throughput phenotypic screening platform where we can investigate the neuronal response to electric field stimulation, EFS, at the network level to assess compound effects on neuronal excitability and synaptic function. During the presentation we will provide a detailed overview of our platform and also present a case study where compound effects on those crucial events are investigated.