论文标题

关键时期和自闭症谱系障碍,睡眠的角色

Critical periods and Autism Spectrum Disorders, a role for sleep

论文作者

Medina, Elizabeth, Peterson, Sarah, Singletary, Kristan, Peixoto, Lucia

论文摘要

大脑的发展依赖于经验和基因定义的程序。某些脑电路特别接受外部刺激而导致可塑性增强的时间窗被称为关键时期。睡眠被认为对于正常的大脑发育至关重要。重要的是,研究表明,睡眠增强了关键时期的可塑性,并促进了发育中的哺乳动物大脑中经验依赖性的突触修剪。因此,关键时期的正常可塑性取决于适当的睡眠。相对于典型发育,自闭症谱系障碍(ASD)的跌倒和入睡问题的发生率更高。在这篇综述中,我们探讨了睡眠,关键时期可塑性和ASD之间的潜在联系。首先,我们回顾了关键时期可塑性在典型发育中的重要性以及睡眠在此过程中的作用。接下来,我们总结了ASD与高浓度ASD基因候选物啮齿动物模型中突触可塑性缺陷联系起来的证据。然后,我们证明几乎所有显示出睡眠不足的ASD的高信任啮齿动物模型也表现出可塑性缺陷。鉴于睡眠对关键时期可塑性的重要性,必须了解ASD中突触可塑性,睡眠和大脑发育之间的联系。但是,缺乏研究ASD小鼠模型中关键时期睡眠或可塑性的研究。因此,我们强调迫切需要考虑在神经发育障碍中睡眠和可塑性研究中的发展轨迹。

Brain development relies on both experience and genetically defined programs. Time windows where certain brain circuits are particularly receptive to external stimuli, resulting in heightened plasticity, are referred to as critical periods. Sleep is thought to be essential for normal brain development. Importantly, studies have shown that sleep enhances critical period plasticity and promotes experience-dependent synaptic pruning in the developing mammalian brain. Therefore, normal plasticity during critical periods depends on proper sleep. Problems falling and staying asleep occur at a higher rate in Autism Spectrum Disorder (ASD) relative to typical development. In this review, we explore the potential link between sleep, critical period plasticity, and ASD. First, we review the importance of critical period plasticity in typical development and the role of sleep in this process. Next, we summarize the evidence linking ASD with deficits in synaptic plasticity in rodent models of high-confident ASD gene candidates. We then show that almost all the high-confidence rodent models of ASD that show sleep deficits also display plasticity deficits. Given how important sleep is for critical period plasticity, it is essential to understand the connections between synaptic plasticity, sleep, and brain development in ASD. However, studies investigating sleep or plasticity during critical periods in ASD mouse models are lacking. Therefore, we highlight an urgent need to consider developmental trajectory in studies of sleep and plasticity in neurodevelopmental disorders.

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