Understanding the mechanisms of epileptogenesis in the hippocampal dentate gyrus using in vivo calcium imaging.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07589
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Jinde Seiichiro 東京大学, 医学部附属病院, 准教授 (30376454)
• Co-Investigator(Kenkyū-buntansha): 菅谷 佑樹 東京大学, 大学院医学系研究科(医学部), 講師 (00625759)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 歯状回 / 苔状細胞 / てんかん / カルシウムイメージング / DREADD

Outline of Final Research Achievements

Mossy cells in the hippocampal dentate gyrus are known to be deeply involved in the pathophysiology of temporal lobe epilepsy, but the exact role of mossy cells has not been elucidated. In the present study, the activity of mossy cells was visualized during epileptic seizures in the awake state by combining the mice that can be genetically engineered specifically for mossy cells with in vivo calcium imaging. The results showed that the activity of mossy cells was largely affected by increased activity along with behavioral epileptic seizures, and that, when the mossy cells was excited, the epileptic activity of granule cells in the dentate gyrus was increased. These studies have revealed a part of the mechanisms of epileptogenesis in temporal lobe epilepsy, and are further expected to lead to the development of new therapies in the future.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

苔状細胞は側頭葉てんかんの特徴的所見である海馬硬化と関連が深いことが知られるが、その機能や役割はこれまでほとんど不明だった。本研究では、てんかん発作の最中に苔状細胞の活動性をリアルタイムで可視化することや、苔状細胞だけの活動をコントロールする技術を用いて、てんかん発作中における苔状細胞の役割の一部を明らかにすることができた。特に苔状細胞の活動性上昇に応じて、海馬歯状回で神経ネットワークを共有する顆粒細胞の同期性の活動が上昇することがわかったことは、側頭葉てんかんの発症のメカニズム解明に近づく結果であり、学術的な意義だけでなく、新たな治療法の開発につながることで社会的にも大きな意義がある。