Analysis of sleep-regulating NMDA receptor signaling conserved in Drosophila and mammals

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08571
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Nagoya City University
• Principal Investigator: Tomita Jun 名古屋市立大学, 医薬学総合研究院(薬学), 講師 (40432231)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 睡眠 / 覚醒 / ショウジョウバエ / 中心複合体 / ドーパミン / NMDA受容体 / カルシニューリン

Outline of Final Research Achievements

We attempted to identify a novel neural circuit in the central complex regulating sleep-wake in Drosophila melanogaster and found a group of protocerebral bridge (PB) interneurons that promote sleep. Because the sleep-promoting PB interneurons had a physical connection with the already identified wake-promoting PB-FB-NO, the PB interneurons should inhibit the PB-FB-NO neurons.
We found that activation of T1 dopaminergic neurons projecting to PB using the temperature-sensitive dTrpA1 channel resulted in a significant reduction in sleep. Dopamine 2-like receptors (Dop2R) knockdown in the sleep-promoting PB interneurons significantly increased sleep, suggesting that T1 dopaminergic neurons promote wakefulness by inhibiting the sleep-promoting PB interneurons through D2 receptor signaling. In addition, we found that NMDA receptor-calcineurin signaling in the sleep-promoting PB interneurons is also involved in sleep regulation.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

同定した睡眠-覚醒を制御する中心複合体PBの神経回路に着目することで、これまで未解明であったNMDA受容体-カルシニューリンシグナルによる睡眠制御の分子機構の解明が可能になる。また、覚醒を促進するT1ドーパミンニューロンは闘争行動の制御に関わることが報告されており、睡眠-覚醒と闘争行動に共通する神経基盤の理解にもつながると期待される。