In our central nervous system (CNS), oligodendrocytes are the specialized glial cells that make the myelin sheaths that provide insulation and trophic support to underlying axons. Myelin also restricts the localization of the ion channels that propagate the nerve impulse to short unmyelinated gaps between consecutive sheaths, called nodes of Ranvier. Although myelination has long been known to accelerate the speed of nerve impulse propagation, in recent years it has become clear that myelin is not simply a static insulator, but a dynamic structure that regulates many aspects of nervous system health and function (reviewed in Chang and others 2016; Fields 2015; Nave and Werner 2014). New myelin in the CNS is made well in to adult life and this occurs by the generation of new myelinating oligodendrocytes (Young and others 2013; Yeung and others 2014), from oligodendrocyte precursor cells (OPCs), which represent about 5% of our mature CNS (Dawson and others 2003), and by the remodeling and renewed growth of existing myelin (Snaidero and others 2014; Yeung and others 2014; Young and others 2013). Myelination can vary throughout the CNS, depending on the time of life, brain area, neuronal subtype, axon diameter (caliber), and the local cellular and molecular microenvironment (reviewed by Tomassy and others 2016). Not only are individual axons either myelinated or not, but the number, distribution, length and thickness of myelin sheaths along axons are all parameters that can vary greatly between myelinated axons. Because myelin accelerates the speed of nerve impulse propagation, some axons may be myelinated simply to speed up communication between specific areas of the CNS. In addition, however, regulation of number, distribution, length, and thickness of myelin sheaths along other axons may be employed to determine precise conduction times. Because the precise timing of communication between neurons affects synaptic plasticity and the functional properties of neuronal ensembles, regulation of myelination has even been proposed as a form of nervous system plasticity (Baraban and others 2016; Fields 2015). Indeed, numerous studies have implicated dynamic alterations of white matter (myelinated axons) as a key regulator of human CNS function. For example, learning how to juggle or intensive practicing of the piano, correlate with changes in white matter in specific areas of the brain, as assessed by magnetic resonance imaging (Bengtsson and others 2005; Scholz and others 2009). Although the cellular correlates of magnetic resonance imaging–based white matter changes are only now beginning to be systematically addressed in model species (e.g., Sampaio-Baptista and others 2013), it is generally assumed that these reflect, at least in part, alterations to myelin (Fields 2015). Work in animal models also supports a role for regulation of myelin in higher order brain function. Social isolation of mice at a specific critical period of postnatal developmental (p21-p35) (Makinodan and others 2012) or for prolonged periods (8 weeks) in adults (Liu and others 2012) can lead to myelin defects and corresponding behavioral phenotypes. Interestingly, genetic knockout of a receptor tyrosine kinase from myelinating oligodendrocytes phenocopies both the myelin defects and behavioral phenotypes caused by postnatal social isolation (Makinodan and others 2012). Treatment with Clemastine, a drug that can promote oligodendrocyte differentiation through activating muscarinic receptor function (F. Mei and others 2014), can rescue the defects caused by social isolation in adult mice (Liu and others 2016a), further suggesting that major phenotypes associated with social isolation are manifest via alterations to myelin. Recent studies have also shown that motor learning promotes the differentiation of myelinating oligodendrocytes in adult mice, and conversely that impairing the ability of adult OPCs to generate new myelinating oligodendrocytes impairs learning (McKenzie and others 2014). In addition to regulation of conduction properties and neuronal circuit function, recent evidence has revealed a role for myelin in providing metabolic support to axons (Simons and Nave 2015). This metabolic support has been shown important for axonal health (Y. Lee and others 2012) and for the maintenance of energetically expensive high-frequency neuronal activity (Saab and others 2016). Disruption to CNS myelin is also known to contribute not only to numerous diseases of the nervous system, including demyelinating diseases such as multiple sclerosis ((Franklin and others 2012), but also to other neurodegenerative and psychiatric conditions (e.g., Jin and others 2015; Kang and others 2013; Nave and Ehrenreich 2014), reflecting our expanding knowledge of the functions of myelinating oligodendrocytes. Despite its importance, our current understanding of how myelination in the CNS is regulated is incomplete. In this review, we will focus on our emerging knowledge of how interactions between axons and oligodendrocytes affect the formation and dynamic regulation of myelination in development and in circuit function.

中文翻译：

---

中枢神经系统髓鞘的轴突调节：结构和功能。

在我们的中枢神经系统（CNS）中，少突胶质细胞是特殊的神经胶质细胞，它们形成髓鞘，为下层的轴突提供绝缘和营养支持。髓磷脂还限制了离子通道的定位，该离子通道将神经冲动传播到连续鞘之间的短无髓间隙，称为兰维耶结节。尽管长期以来人们都知道髓鞘能加速神经冲动的传播速度，但近年来已清楚地认识到，髓鞘不仅是静态的绝缘体，而且是调节神经系统健康和功能的许多方面的动态结构。其他2016年； Fields 2015年； Nave和Werner 2014年）。中枢神经系统中的新髓鞘能很好地适应成年人的生活，这是通过产生新的髓鞘少突胶质细胞而发生的（Young and others 2013； 2012）。Yeung等人，2014年），来自少突胶质细胞前体细胞（OPC），约占我们成熟中枢神经系统的5％（Dawson等人，2003年），以及现有髓磷脂的改造和更新生长（Snaidero等人，2014年； Yeung等人，2014年） ； Young等，2013）。在整个中枢神经系统中，髓鞘形成可能有所不同，这取决于生命的时间，大脑区域，神经元亚型，轴突直径（口径）以及局部细胞和分子微环境（Tomassy等人2016年综述）。不仅单个轴突具有或不具有髓鞘，而且沿轴突的髓鞘的数量，分布，长度和厚度都是在髓鞘轴突之间可以有很大差异的所有参数。由于髓磷脂可加速神经冲动的传播速度，因此某些轴突可能仅被髓鞘化以加速CNS特定区域之间的交流。然而，此外，沿其他轴突的髓鞘鞘的数量，分布，长度和厚度的调节可用于确定精确的传导时间。由于神经元之间精确的交流时机会影响突触可塑性和神经元集成体的功能特性，因此甚至提出将髓鞘调节作为神经系统可塑性的一种形式（Baraban等，2016； Fields，2015）。确实，许多研究都暗示白质（髓鞘轴突）的动态变化是人类中枢神经系统功能的关键调节因子。例如，通过磁共振成像评估，学习如何杂耍或密集练习钢琴与大脑特定区域白质的变化相关（Bengtsson等人，2005年； Scholz等人，2009年）。尽管现在才开始在模型物种中系统地解决基于磁共振成像的白质变化的细胞相关性（例如，Sampaio-Baptista等人，2013），但通常认为这些至少部分反映了对髓磷脂（Fields 2015）。在动物模型中的工作还支持在高级脑功能中调节髓磷脂的作用。在成年后发育的特定关键时期（p21-p35）（Makinodan等人，2012）或成年动物的较长时期（Liu等人，2012）对小鼠进行社会隔离会导致髓磷脂缺陷和相应的行为表型。有趣的是，髓鞘少突胶质细胞表型受体酪氨酸激酶的基因敲除复制了出生后社会隔离引起的髓鞘缺陷和行为表型（Makinodan等人，2012）。克莱默斯汀的治疗可通过激活毒蕈碱受体功能促进少突胶质细胞分化（F. Mei等，2014），可挽救成年小鼠因社交孤立而引起的缺陷（Liu等，2016a），进一步表明主要表型与社会隔离通过髓磷脂的改变得以体现。最近的研究还表明，运动学习可促进成年小鼠髓鞘少突胶质细胞的分化，相反，损害成年OPC产生新的髓鞘少突胶质细胞的能力也会损害学习能力（McKenzie等，2014）。除了调节传导特性和神经元回路功能外，最近的证据还表明髓磷脂在为轴突提供代谢支持中起作用（Simons and Nave 2015）。已显示这种代谢支持对轴突健康很重要（Y. Lee等，2012），对于维持能量上昂贵的高频神经元活动也很重要（Saab等，2016）。众所周知，中枢神经系统髓磷脂的破坏不仅会导致多种神经系统疾病，包括多发性硬化症等脱髓鞘疾病（Franklin等人，2012），还会导致其他神经退行性疾病和精神疾病（例如Jin等人，2015; Kang等，2013年； Nave和Ehrenreich，2014年），这反映了我们对髓鞘少突胶质细胞功能的认识不断增长。我们目前对中枢神经系统髓鞘调控的理解尚不完全。在这篇综述中，我们将集中在轴突和少突胶质细胞之间的相互作用如何影响发育和电路功能中髓鞘形成和动态调节的新兴知识上。