Mechanism of general anesthetic action by controlling locus coeruleus using optogenetics.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08943
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Niigata University
• Principal Investigator: Kurabe Miyuki 新潟大学, 医歯学系, 講師 (30635579)
• Co-Investigator(Kenkyū-buntansha): 佐々木 美佳 岐阜大学, 大学院医学系研究科, 特任講師 (20774061) ; 上野 将紀 新潟大学, 脳研究所, 教授 (40435631)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 青斑核 / 全身麻酔薬 / パッチクランプ法

Outline of Final Research Achievements

The purpose of this study is to elucidate the functional role of the activities of NA/GABA neurons in the locus coeruleus and their interaction during the induction, maintenance, and arousal of general anesthesia, using optogenetic techniques.
To specifically manipulate the locus coeruleus NA neurons, Dbh-Cre mice were used, and AAVs expressing Cre-dependently ChR or ArchR were injected into the locus coeruleus. This enabled us to specifically manipulate NA neurons by exposing the locus coeruleus to specific wavelengths of light. In addition, NA neurons were identified from locus coeruleus slice preparations and patch clamp recordings were performed to examine the effects of propofol on synaptic transmission.

Free Research Field

電気生理学

Academic Significance and Societal Importance of the Research Achievements

今回導入する光遺伝学的手法によってリアルタイムに目的のニューロンの活動をon/offすることが可能となる。これまでのin vitro, in vivoの実験系での問題点を克服し、無麻酔（覚醒）下動物に全身麻酔薬を投与し、リアルタイムに特定のニューロンを操作した際の機能的変化を解析することが可能となる。これらの新たなツールを組み合わせることによって、研究の幅が飛躍的に広がり、従来の知見とは異なる新たな全身麻酔薬の作用機序を見出せると考える。