Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex.
Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex.
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DOI：
10.1523/eneuro.0053-16.2016
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发表时间：
2016-03
期刊：
影响因子：
3.4
通讯作者：
Tononi G
中科院分区：
文献类型：
--
作者：
Billeh YN;Rodriguez AV;Bellesi M;Bernard A;de Vivo L;Funk CM;Harris J;Honjoh S;Mihalas S;Ng L;Koch C;Cirelli C;Tononi G
皮层回路的成熟是分阶段的，从早期的突触发生和突触修剪到晚期的突触完善，形成成人解剖连接基质。由于成熟基质在很大程度上是固定的，干扰其建立的遗传或环境因素会产生不可逆的影响。睡眠中断很少被认为是这些因素之一，以前的研究主要集中在非常年轻的动物身上，以及睡眠剥夺对神经元形态和皮层可塑性的急性影响。青春期是大脑重塑的敏感时期，但青春期的慢性睡眠限制是否对大脑连通性有长期影响尚不清楚。我们使用病毒介导的轴突标记和连续双光子断层扫描来测量来自次级运动皮层（MOs）的全脑投影，这是一个具有弥漫性投影的高阶区域。对于每个MOs目标，我们计算了投射分数，这是对经过的纤维和轴突终端的组合测量，每个目标的大小归一化。我们发现，在青春期早期接受5天CSR的小鼠（P25-P30，每日睡眠减少≥50%，n=14）和未受干扰睡眠的兄弟姐妹（n=14）之间，MOs投影分数没有同质性差异。然而，机器学习算法对动物的分类明显高于偶然水平，这表明两组之间存在差异，但差异是微妙的和异质性的。因此，青春期早期的睡眠中断可能会影响成年后的大脑连接。然而，由于我们的方法依赖于投影密度的全局测量，以前没有用于测量行为操纵引起的连通性变化，因此关于早期CSR的长期结构影响的明确结论需要额外的实验。
Cortical circuits mature in stages, from early synaptogenesis and synaptic pruning to late synaptic refinement, resulting in the adult anatomical connection matrix. Because the mature matrix is largely fixed, genetic or environmental factors interfering with its establishment can have irreversible effects. Sleep disruption is rarely considered among those factors, and previous studies have focused on very young animals and the acute effects of sleep deprivation on neuronal morphology and cortical plasticity. Adolescence is a sensitive time for brain remodeling, yet whether chronic sleep restriction (CSR) during adolescence has long-term effects on brain connectivity remains unclear. We used viral-mediated axonal labeling and serial two-photon tomography to measure brain-wide projections from secondary motor cortex (MOs), a high-order area with diffuse projections. For each MOs target, we calculated the projection fraction, a combined measure of passing fibers and axonal terminals normalized for the size of each target. We found no homogeneous differences in MOs projection fraction between mice subjected to 5 days of CSR during early adolescence (P25–P30, ≥50% decrease in daily sleep, n=14) and siblings that slept undisturbed (n=14). Machine learning algorithms, however, classified animals at significantly above chance levels, indicating that differences between the two groups exist, but are subtle and heterogeneous. Thus, sleep disruption in early adolescence may affect adult brain connectivity. However, because our method relies on a global measure of projection density and was not previously used to measure connectivity changes due to behavioral manipulations, definitive conclusions on the long-term structural effects of early CSR require additional experiments.