| Project/Area Number |
19K19479
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 58040:Forensics medicine-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | sleep / wakefulness / SON / photostimulation / EEG / sleep rebound / supraoptic nuclei / arousal / neurocircuit / seizures / supraoptic nucleus / paraventricula nucleus / channelrhodopsin-2 / NREM sleep / Delta SWS / wakefullness / seizure / cannabinoids / in-situ-hybridization / paraventricular nucleus / CB1RKO / JWH-018 / cannabinoid / signalling pathway / MALDI imaging |
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| Outline of Research at the Start |
We recently published, that agonists of cannabinoid-receptor-1 (CB1R) induce seizures in mice and this convulsive effect is mediated by CB1 receptors. In addition, our data suggest that CB1R agonists activate specific brain area, which could be involved in the development of cannabinoid seizure. Therefore, we aim to identify brain region and signaling pathway involved in the pro-convulsive effect of cannabinoids.
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| Outline of Final Research Achievements |
Initially, this research project aimed to identify brain regions and signaling pathways underlying cannabinoid-induced seizures. Based on previous in-situ hybridization data we assumed that SO nucleus is involved in cannabinoid convulsive effects and therefore investigated the effect of optogenetic activation of SO nucleus. Unexpectedly, we discovered that bilateral photostimulation of SO nuclei did not induce electrographic seizures, but resulted in increased wakefulness (time in wake) with complete absence of sleep (both NREM and REM) during stimulation. Prolonged photostimulation (4 h and more) resulted in complete absence of sleep and produced massive sleep rebound at the end of stimulation. Prolonged photostimulation (8 h) resulted in the absence of sleep for the first 4 hours and significant decrease of sleep for the rest of photostimualtion time. This suggests that SO nucleus is highly involved in inducing and maintaining arousal state.
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| Academic Significance and Societal Importance of the Research Achievements |
Investigation of neural circuit underlying arousal effect of SON photostimulation would provide crucial information on sleep-wake circuitry and the role of hypothalamic SON in maintaining wakefulness
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