Copine-7 is required for REM sleep regulation following cage change or water immersion and restraint stress in mice
Copine-7 is required for REM sleep regulation following cage change or water immersion and restraint stress in mice
复制标题
DOI：
10.1016/j.neures.2020.04.002
复制
发表时间：
2021-03-19
影响因子：
2.9
通讯作者：
Hayashi, Yu
中科院分区：
文献类型：
--
作者：
Liu, Chih-Yao;Tsai, Chia-Jung;Hayashi, Yu
睡眠受环境影响。在啮齿动物中，快速眼动睡眠（REMS）的变化可能先于其他睡眠/觉醒阶段的变化。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外侧核（SLD），它在REMS的调节中起着至关重要的作用。我们寻找在SLD中选择性表达的基因，并确定了Copine-7（Cpne 7），其参与睡眠是完全未知的。我们产生了Cpne 7-Cre敲入小鼠，这使得Cpne 7的敲除（KO）和Cpne 7表达细胞的遗传标记成为可能。虽然Cpne 7-KO小鼠在基础条件下表现出正常的睡眠，但在换笼或水浸和束缚应激后，Cpne 7-KO小鼠中的REMS量大于野生型小鼠，这两种情况都是急性减少REMS的条件。因此，这表明，在某些条件下，Copine-7参与负调节REMS。此外，化学发生激活Cpne 7表达的神经元在SLD减少REMS的量，表明这些神经元负调节REMS。这些结果将SLD中的copine-7和Cpne 7表达神经元鉴定为控制REMS的调节系统的候选分子或神经元组分。(C)2021 Elsevier B. V.和日本神经科学学会。All rights reserved.
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. (C) 2021 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.