Cellular energy dynamics in orexin neurons across sleep-wake cycle

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14756
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: NATSUBORI Akiyo 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主席研究員 (20732837)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: アデノシン3リン酸 (ATP) / 睡眠覚醒 / ファイバフォトメトリー / 生体脳計測

Outline of Final Research Achievements

As one of the regulators of membrane excitability of sleep or arousal-related neurons in animals, the intracellular concentrations of adenosine 5’-triphosphate (ATP), the major cellular energy metabolite, could be involved. In order to test this hypothesis, we conducted in vivo optical recording of intracellular ATP concentration in the lateral hypothalamus, where the orexin neurons involved in arousal is localized, using a genetically encoded fluorescent ATP sensor. With fiber photometric recordings, we observed that intracellular ATP concentrations in the lateral hypothalamus increased during non-REM sleep compared to awake, while a great decrease was observed during REM-sleep of animals. These results showed that intracellular ATP concentrations fluctuates depending on the sleep-wake state of animals. These state-dependent ATP fluctuations could affect neuronal membrane excitability under physiological conditions.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

本研究は、動物の睡眠覚醒に合わせ、細胞のエネルギー分子であるATP（アデノシン3リン酸）が脳内で生理的に変動していることを、マウスを用いた生体計測により明らかにした。特に、動物の覚醒を引き起こす中枢領域である外側視床下部において細胞内ATP濃度が変動していたことから、細胞内ATPが覚醒中枢神経の活動を調節する新たな因子として機能している可能性が予想できる。