Since the guiding principles of Replace, Reduce, and Refine were published, wider context-of-use for alternatives to animal testing have emerged. Induced pluripotent stem cell-derived human glutamatergic-enriched cortical neurons can be leveraged as 2- and 3-dimensional platforms to enable candidate drug screening. Uniquely so, 2-dimensional models are useful considering that they exhibit spontaneous firing, while, 3-dimensional models show spontaneous synchronized calcium transient oscillations. Here, the limitations of selected induced acute seizure models as well as the early utilization of fully differentiated glutamatergic neuron models for interrogation of inducible excitotoxicity following exposure to neuromodulators will be described. The context of use for candidate biomarkers of inducible seizure is also discussed.
Part of the book: Neurotoxins