Evidence for sleep-dependent synaptic renormalization in mouse pups
Evidence for sleep-dependent synaptic renormalization in mouse pups
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DOI：
10.1093/sleep/zsz184
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发表时间：
2019-11-01
期刊：
影响因子：
5.6
通讯作者：
Cirelli, Chiara
中科院分区：
文献类型：
--
作者：
de Vivo, Luisa;Nagai, Hirotaka;Cirelli, Chiara
在青少年和成人大脑中，清醒后突触强度的一些分子、电生理和超微结构测量值高于睡眠后 [1, 2]。这些结果支持这样的观点：睡眠的核心功能是使与清醒期间持续学习相关的突触强度的增加重新正常化，重建细胞稳态并避免失控的增强、突触饱和和记忆干扰 [2, 3]。然而，在青春期之前，当大脑仍在生长并且许多新突触正在形成时，人们普遍认为睡眠可以促进突触的形成和生长。为了评估睡眠对生命早期突触的作用，我们研究了 2 周大的幼鼠（雌雄），它们的大脑仍在经历显着的发育变化，但睡眠和清醒很容易识别。在两种品系（CD-1、YFP-H）中，我们发现幼犬每天有 50% 的时间在睡觉，并且在强制唤醒几个小时后，总睡眠时间立即增加，表明睡眠稳态。然后，在 YFP-H 幼崽中，我们使用连续块面电子显微镜来检查轴突-脊柱界面（ASI）（突触强度的超微结构标记）在清醒和睡眠之间是否发生变化。我们发现，睡眠后皮质突触（第 2 层，运动皮质）的 ASI 相对于长时间清醒后平均小 33.9%，并且条件之间的差异与乘法缩放一致。因此，睡眠依赖性突触重新正常化的需要也可能适用于年轻的、断奶前的大脑皮层，至少在初级运动区的浅层。
In adolescent and adult brains several molecular, electrophysiological, and ultrastructural measures of synaptic strength are higher after wake than after sleep [1, 2]. These results support the proposal that a core function of sleep is to renormalize the increase in synaptic strength associated with ongoing learning during wake, to reestablish cellular homeostasis and avoid runaway potentiation, synaptic saturation, and memory interference [2, 3]. Before adolescence however, when the brain is still growing and many new synapses are forming, sleep is widely believed to promote synapse formation and growth. To assess the role of sleep on synapses early in life, we studied 2-week-old mouse pups (both sexes) whose brain is still undergoing significant developmental changes, but in which sleep and wake are easy to recognize. In two strains (CD-1, YFP-H) we found that pups spend similar to 50% of the day asleep and show an immediate increase in total sleep duration after a few hours of enforced wake, indicative of sleep homeostasis. In YFP-H pups we then used serial block-face electron microscopy to examine whether the axon-spine interface (ASI), an ultrastructural marker of synaptic strength, changes between wake and sleep. We found that the ASI of cortical synapses (layer 2, motor cortex) was on average 33.9% smaller after sleep relative to after extended wake and the differences between conditions were consistent with multiplicative scaling. Thus, the need for sleep-dependent synaptic renormalization may apply also to the young, pre-weaned cerebral cortex, at least in the superficial layers of the primary motor area.