Molecular and functional analysis of neural network of the circadian clock

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15921
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: University of Tsukuba
• Principal Investigator: Hirano Arisa (平野有沙) 筑波大学, 医学医療系, 助教 (60806230)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 概日時計 / 概日リズム / 視交叉上核 / SCN

Outline of Final Research Achievements

The suprachiasmatic nucleus is known as a master circadian clock regulating the circadian rhythms. In this study, we tried to identified the neuronal circuits generating the sleep-wake cycle and body temperature cycle and their physiological functions. By using virus vectors, we inhibited the neuronal transmission by expression of tetanus toxin light-chain in neurons projecting the preoptic area and found that this pathway is important for generation of sleep-wake pattern in mice. Interestingly, we also found that the mice still exhibited the wheel-running rhythms, suggesting that there are distinct pathways to regulate sleep-wake and wheel-running activity rhythms, although these are closely related. We also found that the oscillation of PER2, one of core clock proteins, was not affected in mice, which lost rhythmicity at the behavioral level. This result indicated that we succeeded to manipulate the output of the clock neuron for sleep-wake cycle rather than the oscillators.

Free Research Field

時間生物学

Academic Significance and Societal Importance of the Research Achievements

本研究領域では、時計中枢である視交叉上核内における神経カップリングや、神経内の分子振動に関する研究が多い。一方で、神経から他の脳領域に出力して生理リズムを生み出す神経機構には多くの謎が残されている。本研究は、睡眠リズムおよび体温リズムを生み出す出力機構の一端を明らかにしたという意味で先駆的な研究である。これらの出力経路の理解は、概日時計そのものをターゲットとしない睡眠障害に対する介入法の開発に役立つと期待できる