| Project/Area Number |
22K20501
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0403:Biomedical engineering and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Chow Siu Yu 東京大学, 生産技術研究所, 特任助教 (90966590)
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Organoid / Neuron / Dopamine / Midbrain / Schizophrenia / Cerebral / Reward learning / オルガノイド / ドーパミン / 神経細胞 / 神経回路 / 報酬学習 / ヒトiPS細胞 / 統合失調症 / 中脳⽪質回路 / iPS細胞 |
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| Outline of Research at the Start |
本研究では試験管内で大脳と中脳がつながる回路を模倣した培養神経回路組織を作製し、その成り立ちと機能について調べることを目的とする。機能性（神経活動）に加えて、構造的・細胞的解析を行い、報酬学習において重要なネットワーク接続の基礎となる生物学を理解することを目指す。また、関連する疾患を理解するために活用する方法を開発したい。
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| 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.
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| 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。
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