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Copine-7 is required for REM sleep regulation following cage change or water immersion and restraint stress in mice
Neuroscience Research ( IF 2.9 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.neures.2020.04.002
Chih-Yao Liu 1 , Chia-Jung Tsai 1 , Shinnosuke Yasugaki 2 , Nanae Nagata 3 , Miho Morita 3 , Ayako Isotani 4 , Masashi Yanagisawa 5 , Yu Hayashi 6
Affiliation  

Sleep is affected by the environment. In rodents, changes in the amount of rapid eye movement sleep (REMS) can precede those of other sleep/wake stages. The molecular mechanism underlying the dynamic regulation of REMS remains poorly understood. Here, we focused on the sublaterodorsal nucleus (SLD), located in the pontine tegmental area, which plays a crucial role in the regulation of REMS. We searched for genes selectively expressed in the SLD and identified copine-7 (Cpne7), whose involvement in sleep was totally unknown. We generated Cpne7-Cre knock-in mice, which enabled both the knockout (KO) of Cpne7 and the genetic labeling of Cpne7-expressing cells. While Cpne7-KO mice exhibited normal sleep under basal conditions, the amount of REMS in Cpne7-KO mice was larger compared to wildtype mice following cage change or water immersion and restraint stress, both of which are conditions that acutely reduce REMS. Thus, it was suggested that copine-7 is involved in negatively regulating REMS under certain conditions. In addition, chemogenetically activating Cpne7-expressing neurons in the SLD reduced the amount of REMS, suggesting that these neurons negatively regulate REMS. These results identify copine-7 and Cpne7-expressing neurons in the SLD as candidate molecular or neuronal components of the regulatory system that controls REMS.

中文翻译:

Copine-7 是小鼠换笼或水浸和约束应激后 REM 睡眠调节所必需的

睡眠受环境影响。在啮齿动物中,快速眼动睡眠 (REMS) 量的变化可能先于其他睡眠/清醒阶段的变化。REMS动态调节的分子机制仍然知之甚少。在这里,我们专注于位于脑桥被盖区的背侧核(SLD),它在REMS的调节中起着至关重要的作用。我们搜索了在 SLD 中选择性表达的基因,并确定了 copine-7 (Cpne7),其参与睡眠是完全未知的。我们生成了 Cpne7-Cre 敲入小鼠,这使得 Cpne7 的敲除 (KO) 和表达 Cpne7 的细胞的基因标记成为可能。虽然 Cpne7-KO 小鼠在基础条件下表现出正常睡眠,与野生型小鼠相比,Cpne7-KO 小鼠在换笼或浸水和约束压力后的 REMS 量更大,这两种情况都会急剧减少 REMS。因此,有人提出 copine-7 在某些条件下参与了 REMS 的负调节。此外,化学遗传学激活 SLD 中表达 Cpne7 的神经元减少了 REMS 的数量,表明这些神经元负调节 REMS。这些结果将 SLD 中表达 copine-7 和 Cpne7 的神经元确定为控制 REMS 的调节系统的候选分子或神经元成分。化学遗传学激活 SLD 中表达 Cpne7 的神经元减少了 REMS 的数量,表明这些神经元负调节 REMS。这些结果将 SLD 中表达 copine-7 和 Cpne7 的神经元确定为控制 REMS 的调节系统的候选分子或神经元成分。化学遗传学激活 SLD 中表达 Cpne7 的神经元减少了 REMS 的数量,表明这些神经元负调节 REMS。这些结果将 SLD 中表达 copine-7 和 Cpne7 的神经元确定为控制 REMS 的调节系统的候选分子或神经元成分。
更新日期:2020-04-01
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