Neuronal circuit for sedative/hypnotic actions of alpha-2 adrenergic agonist

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20699
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: Toho University
• Principal Investigator: Yamagata Tomoko 東邦大学, 医学部, 助教 (90584433)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 睡眠 / 鎮静 / α２作動薬 / デクスメデトミジン / マウス

Outline of Final Research Achievements

Dexmedetomidine, an alpha 2 agonist, is widely used in clinical practice as a pre- and post-operative sedative, but it remains unclear how it exerts its sedative effects and why it induces deep non-REM sleep-like EEG and inhibits REM sleep. To this end, this study aimed to elucidate the neuronal mechanism of sedation by dexmedetomidine (DEX), an adrenergic α2-receptor agonist, using pharmacogenetic and photogenetic methods. By using a genetical method to visualize specific neuronal cell populations in an activity-dependent manner (TRAP), we identified cell populations that are activated by DEX. We further manipulated those cell populations pharmacogenetically and optogenetically and examined the causal role of those cells on sedation and sleep/arousal.

Free Research Field

神経生物学

Academic Significance and Societal Importance of the Research Achievements

α２作動薬のデクスメデトミジンは、術前・術後の鎮静薬として臨床の場でひろく使われているが、どのように鎮静作用が出現するのか、また、なぜこの薬による鎮静が深いノンレム睡眠様の脳波を誘発し、かつレム睡眠を抑制するかは不明なままである。本研究は、鎮静時に活性化される神経回路についてその睡眠・覚醒への役割を検証した。鎮静と睡眠・覚醒の神経基盤について明らかにしたという点で、学術的に意義がある。