Identification and analyses of molecules and neural circuits regulating REM sleep

调节快速眼动睡眠的分子和神经回路的识别和分析

• 批准号: 18J11827
• 负责人: Liu ChihーYao
• 金额: $ 0.96万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2018
• 资助国家: 日本
• 起止时间: 2018-04-25 至 2020-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18J11827/
• 关键词: Rapid-eye-movement sleep; Sublaterodorsal nucleus; Cpne7; Copine-7

Mammalian sleep is composed of rapid-eye-movement (REM) sleep and non-REM (NREM) sleep. REM sleep is particularly susceptible to various external factors or diseases. Although several genes are associated with REM sleep, the relationship between the products of these genes and the brain areas critical for regulating REM sleep remains poorly understood. Moreover, the molecular mechanisms underlying changes in REM sleep caused by environmental factors are unclear. Here, I focused on Cpne7, as a gene that is highly expressed in the sublateral dorsal nucleus (SLD), a brain area critical for generating REM sleep in rodents. The function of the product of Cpne7, copine-7 in the brain was unknown. Therefore, I generated a Cpne7-Cre knock-in mouse line that allows us to examine the effect of deleting Cpne7 and to genetically label and manipulate cells that express Cpne7. As a results, I found the baseline sleep was not changed in Cpne7-KO mice. However, the amount of REM sleep was more in Cpne7-KO mice following cage change or water immersion and restraint stress, both of which are conditions that acutely reduce REM sleep, suggesting copine-7 is involved in the regulation of REM sleep under certain conditions. Moreover, chemogenetic activation of Cpne7-expression neurons in the SLD reduced the amount of REM sleep, suggesting these neurons negatively regulate REM sleep. Collectively, these results suggest copine-7 and Cpne7-expressing neurons in the SLD as candidate molecular or neuronal components of the regulatory system that controls REM sleep.

哺乳动物的睡眠分为快速眼动（REM）睡眠和非快速眼动（NREM）睡眠。REM睡眠特别容易受到各种外部因素或疾病的影响。虽然有几个基因与REM睡眠有关，但这些基因的产物与调节REM睡眠的关键大脑区域之间的关系仍然知之甚少。此外，由环境因素引起的REM睡眠变化的分子机制尚不清楚。在这里，我专注于Cpne 7，作为一种在下外侧背核（SLD）中高度表达的基因，这是啮齿动物产生REM睡眠的关键大脑区域。Cpne 7的产物copine-7在脑中的功能尚不清楚。因此，我产生了一个Cpne 7-Cre敲入小鼠系，使我们能够检查删除Cpne 7的影响，并遗传标记和操纵表达Cpne 7的细胞。结果，我发现Cpne 7-KO小鼠的基线睡眠没有改变。然而，在换笼或浸水和束缚应激后，Cpne 7-KO小鼠的REM睡眠量更多，这两种情况都是急性减少REM睡眠的条件，这表明copine-7在某些条件下参与了REM睡眠的调节。此外，在SLD中Cpne 7表达神经元的化学发生激活减少了REM睡眠的量，表明这些神经元负调节REM睡眠。总的来说，这些结果表明，在SLD中的copine-7和Cpne 7表达神经元作为控制REM睡眠的调节系统的候选分子或神经元成分。

项目成果

Genetic analyses of molecules and neural circuits regulating REM sleep

调节快速眼动睡眠的分子和神经回路的遗传分析

• 发表时间: 2019
• 作者: Chih-Yao Liu;Chia-Jung Tsai;Shinnosuke Yasugaki;Nanae Nagata;Miho Morita;Ayako Isotani;Masashi Yanagisawa;and Yu Hayashi.;Chih-Yao Liu
• 通讯作者: Chih-Yao Liu

Copine-7 is required for REM sleep regulation following cage change or water immersion and restraint stress in mice

• DOI: 10.1016/j.neures.2020.04.002
• 发表时间: 2021-03-19
• 期刊: NEUROSCIENCE RESEARCH
• 影响因子: 2.9
• 作者: Liu, Chih-Yao;Tsai, Chia-Jung;Hayashi, Yu
• 通讯作者: Hayashi, Yu