Construction of an iPS cell-derived mesocortical circuit in vitro

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20501
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0403:Biomedical engineering and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Chow Siu Yu 東京大学, 生産技術研究所, 特任助教 (90966590)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: Organoid / Neuron / Dopamine / Midbrain / Schizophrenia / Cerebral / Reward learning

Outline of Final Research Achievements

In this study, we developed a method to construct a model of the mesocortical circuit in vitro by culturing iPSC-derived cerebral and midbrain organoids inside a custom-made microdevice. Differentiated cerebral and midbrain organoids were placed into two chambers of the device. Axons grow and extend into a channel, eventually forming a bundle connecting the two organoids. Successful differentiation of the organoids was confirmed with immunostaining. Using multi-electrode arrays (MEAs), we recorded and compared the activity of the cerebral and midbrain organoids and observed that although the two organoids have a comparable number of spikes, they exhibit different activity patterns. Upon connection, we observed the propagation of activity from one organoid to another, indicating that a functional connection has been established in our circuit. Interestingly, we further found that the propagating activity was mostly initiated by cerebral organoids and received by midbrain organoids.

Free Research Field

神経科学、組織工学

Academic Significance and Societal Importance of the Research Achievements

中脳皮質回路は報酬学習や統合失調症などの疾患において重要である。試験管内で中脳皮質回路の開発により、試験管内で中脳皮質回路の構造、細胞、機能の分析を実施し、報酬学習に重要なネットワーク接続の根底にある生物学を理解することができる。患者由来の iPS 細胞を使用して、この回路を疾患モデルとして使用し、統合失調症などの疾患が中皮質回路にどのように影響するかを明らかにし、将来の医薬品の開発に役立てることもできる。