Epileptic activity through excitatory/inhibitory imbalance observed in neuronal networks cultured on micro-electrode arrays

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H04437
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: The University of Tokyo
• Principal Investigator: Jimbo Yasuhiko 東京大学, 大学院工学系研究科(工学部), 教授 (20372401)
• Co-Investigator(Kenkyū-buntansha): 榛葉 健太 東京大学, 大学院工学系研究科(工学部), 助教 (80792655)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脳神経 / 細胞・組織 / 神経工学 / 微小電極アレイ

Outline of Final Research Achievements

Focusing on the excitatory/inhibitory (E/I) balance of neuronal circuits, which is considered to be the "final common path" in the process of epileptic seizure generation, we constructed cultured neuronal networks with artificially controlled E/I balance and recorded electrical activity using micro-electrode array (MEA) substrates. Pharmacological manipulation (administration of agonists and antagonists to the SHH pathway) during the differentiation of mouse iPS cells into cortical cells enabled control of the ratio of excitatory cells in the range of 50-80%, and E/I balance-dependent changes in synchronized burst activity characteristics were observed. The experimental results suggest that activity-dependent plasticity as well as homeostatic plasticity may be involved in the regulation of synaptic strength, which affects the network-activity properties.

Free Research Field

神経工学

Academic Significance and Societal Importance of the Research Achievements

EIバランスと神経回路活動の関係は，興奮性／抑制性シナプス結合の数とその強度によって制御されるが，電気刺激等人工的な手法で誘起されるシナプス活動と本来の感覚入力に対して活性化されるシナプスは異なる，興奮性シナプス，抑制性シナプス，そのサブタイプそれぞれにおいて可塑性のメカニズムが異なるなど関係する要素は多岐にわたる．本研究では恒常性を維持する可塑性の関与を示唆する結果が得られた．今後は，シナプス－ニューロン－神経回路という階層構造各段階における制御機構，その背景となる可塑性の作用を統合した研究の遂行により，てんかん発作を生じるメカニズム解明に向けた知見が得られることが期待できる．