Host: The Japanese Society of Toxicology
Name : The 47th Annual Meeting of the Japanese Society of Toxicology
Date : 2020 -
Human induced pluripotent stem cell (iPSC)-derived neurons can be used to predict neurotoxicity and CNS drug efficacy by measuring their activity with recording systems such as multielectrode arrays (MEAs). However, most of the current methods rely on uniform cultures of randomly mixed neurons, which might not be representative of the complexity of brain networks. Here we investigate how network organization affects electrical responses of cultured iPSC-derived neurons.
Several types of neuronal populations were generated by transcription factor-induced differentiation of iPSCs and were shown to exhibit specific and reproducible spontaneous burst profiles when cultured individually. Then, using micropatterning processes, distinct neuronal populations were arranged in separate areas of a MEA. Co-cultured neuronal clusters synchronized their firing activity over time, indicating that synaptic connections occurred both within and among the neuronal clusters. These micropatterned structures were further evaluated for their response to neurotransmitter receptor blockers and for the functional recovery of connectivity following axonal injury.
Our results show that monitoring the activity of neuronal clusters allows to evaluate the dynamic changes in neurotransmission induced by network regulation or disruption and their effects on pharmacological responses. Thus, the combination of robust neuronal differentiation methods with microengineering techniques should lead to the development of new in vitro models that are physiologically more relevant to in vivo brain functions.
