Light as a central modulator of circadian rhythms, sleep and affect.
Light as a central modulator of circadian rhythms, sleep and affect.
复制标题
DOI：
10.1038/nrn3743
复制
发表时间：
2014-07
影响因子：
34.7
通讯作者：
Hattar, Samer
中科院分区：
文献类型：
--
作者：
LeGates, Tara A.;Fernandez, Diego C.;Hattar, Samer
视网膜感光器将光能转换成电子信号，从而启动视觉。经典的光感受器，视杆细胞和视锥细胞，具有修饰的纤毛，纤毛由光色素（视紫红质和视锥蛋白）集中的膜堆组成。杆状细胞非常敏感，甚至能探测到几个光子。因此，视杆细胞用于夜视。视锥细胞不如视杆状细胞敏感，用于感知白天和颜色。色觉是由锥体光感受器介导的，锥体光感受器表达锥体视蛋白，在不同波长（颜色）的光下具有灵敏度峰值。人类有三种视锥细胞：短波、短波和长波敏感视锥细胞（为了简单起见，我们将它们分别称为蓝色、绿色和红色视锥细胞）。视杆细胞和视锥细胞通过多突触通路将光信息传递给视网膜神经节细胞（RGCs）， RGCs支配大脑的不同区域进行复杂的视觉处理。一项令人惊讶的发现表明，RGCs的一个亚群具有内在的光敏性，并表达光色素黑视素。这些细胞因此被称为iprgc。黑视素基因（Opn4）最初是从非洲爪蟾的皮肤黑色素细胞中克隆出来的，并且在包括人类在内的许多哺乳动物物种中都有同源物。序列分析表明，与脊椎动物的视蛋白相比，黑视素与无脊椎动物的视蛋白具有更多的同源性，这表明黑视素可能使用不同于脊椎动物视杆细胞和视锥细胞中存在的光色素的光信号传导机制。ipRGCs不具有光色素可浓缩的修饰膜，因此，黑视素蛋白在整个体细胞、树突和轴突初始段均匀表达。缺乏膜专门化使得iprgc对光的敏感度低于杆状细胞和锥状细胞。然而，iprgc能够在很长一段时间内吸收光信号，从而在长时间的光刺激下增加其灵敏度。iprgc对光谱蓝色区域的光波长最为敏感。作为神经节细胞，ipRGCs除了其固有的依赖黑视素的途径外，还可以传递来自视杆细胞和视锥细胞的光信息，并可以控制各种光介导的行为。最初，ipRGCs被认为是一个统一的种群，然而，最近的发现表明，ipRGCs是高度多样化的，根据形态和电生理分析，在啮齿动物中至少包括5种不同的亚型（M1-M5）。最初确定的群体现在被称为M1 ipRGCs，主要投射到涉及非图像形成视觉功能的大脑区域，而非M1 ipRGCs则广泛投射到大脑中对图像形成重要的区域。ipRGC亚型表达不同水平的黑视素蛋白，并且在内丛状层（IPL）中具有不同的树突分层模式，这表明每种亚型在内在检测光和向大脑发送杆状和锥状信息的过程中可能发挥特定作用。光深刻地影响了地球上生命的进化。众所周知，光可以让我们生成环境的图像。然而，光，通过非典型的内在光敏视网膜神经节细胞（ipRGCs；框1），也影响对我们的健康和生活质量至关重要的行为，但与图像形成无关。其中包括生物钟与太阳日的同步，季节变化的跟踪，以及睡眠的调节。不规则的光线环境会导致昼夜节律和睡眠问题，最终导致情绪和学习障碍。最近，人们发现不规则的光线也可以直接影响情绪和学习，而不会对昼夜节律和睡眠产生重大干扰。在这里，我们将讨论光对情绪和学习的间接和直接影响，并为光、生物钟和睡眠如何相互作用影响情绪和认知功能提供一个模型。
Retinal photoreceptors transduce light energy into electrical signals that initiate vision. The classical photoreceptors, rods and cones, possess modified cilia that consist of stacks of membranes in which photopigments (rhodopsin and cone opsins) are concentrated. Rods are exquisitely sensitive and are able to detect even a few photons. Rods are therefore used for night vision. Cones are less sensitive than rods and are used for day and color vision. Color vision is mediated by cone photoreceptors that express cone-opsins with sensitivity peaks at different wavelengths (colors) of light. Humans have three cone types: short, mid and long wavelength sensitive cones (for simplicity, we will refer to these as blue, green and red cones, respectively). Rods and cones relay photic information through multisynaptic pathways to retinal ganglion cells (RGCs), which innervate different areas in the brain for complex visual processing. A surprising discovery showed that a subpopulation of RGCs is intrinsically photosensitive and express the photopigment melanopsin. These cells were thus termed ipRGCs. The melanopsin gene (Opn4) was originally cloned from Xenopus laevis dermal melanophores, and was shown to have orthologs in many mammalian species, including humans. Sequence analysis shows that melanopsin shares more homology with invertebrate opsins than with vertebrate opsins, suggesting that melanopsin may use a different mechanism for light signaling than that used by the photopigments present in the rods and cones of vertebrates. ipRGCs do not have modified membranes in which the photopigment can be concentrated: thus, melanopsin protein is expressed uniformly throughout the soma, dendrites, and the initial segment of the axon. The lack of membrane specialization makes ipRGCs less sensitive to light than rods and cones. However, ipRGCs are able to incorporate light signals over extended period of time, resulting in an increase in their sensitivity during prolonged light stimulation. ipRGCs are most sensitive to wavelengths of light that are in the blue region of the light spectrum. As ganglion cells, ipRGCs also convey light information from rods and cones in addition to their intrinsic melanopsin-dependent pathway and can control a variety of light-mediated behaviors. Originally, ipRGCs were thought to comprise a uniform population, however, recent discoveries revealed that ipRGCs are highly diverse, comprising at least five distinct subtypes (M1-M5) in rodents based on morphological and electrophysiological analyses. The originally identified population is now known as M1 ipRGCs and project predominantly to brain regions involved in non-image forming visual functions, whereas the non-M1 ipRGCs show widespread projections to areas in the brain important for image formation. ipRGC subtypes express varying levels of the melanopsin protein and have different patterns of dendrite stratification in the inner plexiform layer (IPL), indicating that each subtype could play a particular role in detecting light intrinsically and in signaling rod and cone information to the brain. Light has profoundly influenced the evolution of life on earth. As widely appreciated, light allows us to generate images of our environment. However, light, through the atypical intrinsically photosensitive retinal ganglion cells (ipRGCs; Box 1), also influences behaviors that are essential for our health and quality of life, yet are independent of image formation. These include the synchronization of the circadian clock to the solar day, tracking of seasonal changes, and regulation of sleep. Irregular light environments lead to problems in circadian rhythms and sleep, which eventually cause mood and learning deficits. Recently, it was found that irregular light can also directly impact mood and learning without producing major disruptions in circadian rhythms and sleep. Here, we will discuss the indirect and direct influence of light on mood and learning and provide a model for how light, the circadian clock, and sleep interact to influence mood and cognitive functions.
登录
查看更多内容
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
6.7
作者：
Anderson, J. L.;Glod, C. A.;Lockley, S. W.
通讯作者：
Lockley, S. W.
影响因子：
9.8
作者：
Bellingham, James;Chaurasia, Shyam S.;Lucas, Robert J.
通讯作者：
Lucas, Robert J.
影响因子：
5.3
作者：
Benedetti, F;Colombo, C;Smeraldi, E
通讯作者：
Smeraldi, E
DOI：
10.1073/pnas.0808312105
发表时间：
2008-12-16
影响因子：
11.1
作者：
Altimus, C. M.;Guler, A. D.;Hattar, S.
通讯作者：
Hattar, S.