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

Yuya Sato; Hideaki Yamamoto; Hideyuki Kato; Takashi Tanii; Shigeo Sato; Ayumi Hirano-Iwata

doi:10.3389/fnins.2022.943310

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

Front Neurosci. 2023 Jan 9:16:943310. doi: 10.3389/fnins.2022.943310. eCollection 2022.

Authors

Yuya Sato^{1

2}, Hideaki Yamamoto¹, Hideyuki Kato³, Takashi Tanii⁴, Shigeo Sato¹, Ayumi Hirano-Iwata^{1

2

5}

Affiliations

¹ Research Institute of Electrical Communication, Tohoku University, Sendai, Japan.
² Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
³ Faculty of Science and Technology, Oita University, Oita, Japan.
⁴ Faculty of Science and Engineering, Waseda University, Tokyo, Japan.
⁵ Advanced Institute for Materials Research, Tohoku University, Sendai, Japan.

Abstract

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 a 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.

Keywords: cell engineering; complex networks; cultured neuronal network; microelectrode array (MEA); microfluidic devices.

Grants and funding

This study was supported by the Cooperative Research Project Program of Research Institute of Electrical Communication (RIEC), Tohoku University, MEXT KAKENHI Grant-in-Aid for Transformative Research Areas (B) “Multicellular Neurobiocomputing” (21H05163 and 21H05164), JSPS KAKENHI (20K20550, 20H02194, 21K12050, 22H03657, and 22K19821), JST-PRESTO (JMPJPR18MB), JST-CREST (JPMJCR19K3), and the Basic Science Research Grant from the Sumitomo Foundation.