Objective

The lack of advancement in anti-epileptic drugs (AEDs) over the last 30 years, along with the continued need for improved proconvulsant screening in drug safety, motivates the need for new assays of seizurogenic neural activity.  Previous work has established an in vitro approach for detecting and quantifying seizurogenic activity using multiwell microelectrode array (MEA) technology, providing a predictive and high-throughput avenue for the evaluation of the efficacy of AEDs and the proconvulsant risk of other drug candidates.  Here, we present an updated assay of seizurogenic activity based upon guidelines developed in the HESI NeuTox consortium, which is a collection of academic, commercial, and pharmaceutical representatives working towards the development of in vitro assessment of proconvulsant risk.  We used previously published metrics for the detection of burst spiking events and the quantification of synchronization across a neural population, in spontaneous and evoked conditions.  Data are included from cryopreserved rat cortical neurons evaluated with the 10 compounds selected by the NeuTox consortium, which include reference compounds with known proconvulsant risk via multiple mechanisms and negative control compounds.  Our results support the combined use of evoked and spontaneous neural activity, collected using multi-well MEA technology, for the high throughput evaluation of complex neuronal networks in vitro to quantify the proconvulsant risk of candidate pharmaceuticals in a pre-clinical setting.