Although further optimization and upscaling is necessary the presented neuron-astrocyte co-culture model could be used to screen for compounds that affect network functionality, either acute or chronically, in the context of phenotypic neurotoxicity screening. Due to the high sensitivity of the calcium assay, subtle changes in network activity might be detected, while other readouts like neurite outgrowth are still unaffected7. These combined readouts, in high-content format, allow for gauging neuronal networks. Furthermore, the model might offer a valuable tool for preclinical research and to screen for compounds that restore proper network functionality and reduce the progression of neuronal pathologies that display disturbed network activity and connectivity. For example, the potential mechanisms underlying the lack of neural synchronicity observed in schizophrenia15 could be explored. Increased bursting frequency and synchronized oscillations as seen in Parkinson’s disease50, FTD5152 and epilepsy111314 and more complex dysregulation of network function as reported in Alzheimer’s disease1153 and autism (reviewed in ref. 10) could be studied as well.
