Microfluidic cell engineering on high-density microelectrode arrays for assessing structure-function relationships in living neuronal networks

Neuronal networks in dissociated culture combined with cell engineering technology offer a pivotal platform to constructively explore the relationship between structure and function in living neuronal networks. Here, we fabricated defined neuronal networks possessing a modular architecture on high-density microelectrode arrays (HD-MEAs), a state-of-the-art electrophysiological tool for recording neural activity with high spatial and temporal resolutions. We first established a surface coating protocol using a cell-permissive hydrogel to stably attach polydimethylsiloxane microfluidic film on the HD-MEA. We then recorded the spontaneous neural activity of the engineered neuronal network, which revealed an important portrait of the engineered neuronal network--modular architecture enhances functional complexity by reducing the excessive neural correlation between spatially segregated modules. The results of this study highlight the impact of HD-MEA recordings combined with cell engineering technologies as a novel tool in neuroscience to constructively assess the structure-function relationships in neuronal networks.