2018 Fiscal Year Annual Research Report
Elucidation of the molecular mechanisms of zinc-induced sleep
| Project/Area Number |
16K18698
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| Research Institution | University of Tsukuba |
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Principal Investigator |
シェラス ヨアン 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (60544319)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | Sleep / zinc / optogenetics / DREADD |
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| Outline of Annual Research Achievements |
Sleep is so essential to every animal that a complete sleep deprivation is leading to a quick death. The elementary mechanism regulating sleep (which remains unknown) must be very simple and present in every organism. In a previous study, we examined the sleep-promoting activity of zinc by monitoring locomotor activity and electroencephalogram after oral administration to mice at the onset of dark time. Compared with the placebo group, zinc-containing yeast extract as well as zinc gluconate dose-dependently reduced locomotor activity and increased the total amount of non-rapid eye movement (NREM) sleep in mice.
To better understand the molecular mechanisms of zinc-induced sleep, we then performed a c-fos mapping 1 hour after zinc administration. We discovered a subset of neurons activated into a specific area of the extended amygdala. After expressing DREADD receptors specifically in these neurons, chemogenetic activation (DREADD hM3Dq) increased the amount of NREM sleep, while their chemogenetic inhibition (DREADD hM4Di) could partially block the zinc-induced sleep. These results demonstrate the ability for these neurons to modulate the amount of NREM sleep.
Further experiments using optogenetics allowed for a better time-controlled experiment. Optogenetic stimulation efficiently increased the amount of NREM sleep during the 2 hours following the stimulation, confirming previous data. Furthermore, tracing experiment discovered projections from zinc-sensitive neurons into the medial septum. This data illustrating the potential discovery of a new sleep regulating pathway.
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