Multi-electrode array (MEA) assays using human induced pluripotent stem cell (hiPSC)-derived neurons are expected to predict the convulsion toxicity of new drugs. Although the balance between excitatory and inhibitory inputs is important in convulsive seizure, the optimal proportion is not known. In this study, we evaluated the spontaneous firing properties and the responses to convulsants in hiPSC-derived cortical neuronal network, in which the ratio of Glutamatergic (Glu) and GABAergic (GABA) neurons are 88 : 12, 84 : 16, 74 : 26, 58 : 42, and 48 : 52. The network with a high percentage of excitatory neurons showed short synchronized burst firings (SBFs) in spontaneous firings. On the other hand, the network with high inhibitory neurons showed the SBF with long period. In drug-induced seizure activities, there was no remarkable dose responses in high percentage of excitatory neurons. On the other hand, the network with high inhibitory neurons showed significant activity changes with a lot of convulsants regardless of GABA receptor inhibitor. These results suggest that a higher proportion of GABA neurons compared with real brain is more effective in detecting drug-induced seizure toxicity.

To: 要旨(抄録)