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Reading 3 Why We Sleep: A Biological Perspective 从生物学角度考察人类为什么要睡眠By Jerome M. SiegelSection 1 1 Birds do it, bees do it, and even fruit flies appear to do it. Humans certainly do it. The subject is not love, but sleep. Shakespeares Macbeth said it “knits up the raveled sleeve of care” and was the balm of hurt minds, great natures second course, chief nourisher in lifes feast. Cervantess Sancho Panza sang its praises as the food that cures all hunger, the water that quenches all thirst, the fire that warms the cold, the cold that cools the heart. the balancing weight that levels the shepherd with the king, and the simple with the wise. 鸟儿/蜜蜂儿/甚至是苍蝇儿都需要睡觉,人类当然也需要睡觉.本主题所谈论的非爱情,而是睡眠.莎士比亚说,那是”织补关照的袖口”和那是”心灵慰藉,自然的赋予,生命的滋养”科文特斯.伯查却赞歌”食足肚饿,水慰口渴,火暧冬寒,寒静热血.这均衡的赐予抚平了牧人与国王的差别,抚平了愚者与智者的差别.”2 The simple and the wise have long contemplated two related questions: What is sleep, and why do we need it? An obvious answer to the latter is that adequate sleep is necessary to stay alert and awake. That response, however, dodges the issue and is the equivalent of saying that you eat to keep from being hungry or breathe to ward off feelings of suffocation. The real function of eating is to supply nutrients, and the function of breathing is to take in oxygen and expel carbon dioxide. But we have no comparably straightforward explanation for sleep. That said, sleep research - less than a century old as a focused field of scientific inquiry - has generated enough insight for investigators to at least make reasonable proposals about the function of the somnolent state that consumes one third of our lives. 人们长期关注着两个相关的问题:什么是睡眠,为什么要睡眠?一个最新的答案是:睡眠是为了保持警觉和清醒的需要.然后,这个答案回避了问题本身,如同说吃饭是为了充饥,呼吸是为了免除窒息一样.其实,吃饭的作用是提供营养,呼吸的作用是吸入氧气和呼出二氧化碳.但我们没有同样地直接回答睡眠是为了什么.也就是说, 人们对睡眠的研究,在不到一个世纪以来将之作为一个重要的研究领域已经进行了充分的探究,至少对于这一占去人生三分之一的睡眠的功能提出了合理的解释.Section 2 What is sleep?3 Despite the difficulty in strictly defining sleep, an observer can usually tell when a subject is sleeping: the sleeper ordinarily exhibits relative inattention to the environment and is usually immobile. (Dolphins and other marine mammals swim while sleeping, however, and some birds may sleep through long migrations.) 尽管严格定义睡眠是困难的.但是观测者一般能看出什么时候是进入睡眠状态:睡眠者通常对环境失去注意,以及静止不动.4 In 1953 sleep research pioneer Nathaniel Kleitman and his student Eugene Aserinsky of the University of Chicago decisively overthrew the commonly held belief that sleep was simply a cessation of most brain activity. They discovered that sleep was marked by periods of rapid eye movement, commonly now known as REM sleep. And its existence implied that something active occurred during sleep. All terrestrial mammals have been examined exhibit REM sleep, which alternates with non-REM sleep, also called quiet sleep, in a regular cycle. 睡眠研究的先行者芝加哥大学的纳撒尼尔与他的学生尢金在1953年果断地推翻以往认为睡眠是大部分大脑活动的简单停止的观点.他们发现睡眠是以快速动眼期开始的活动,现在通常称作快速动眼期睡眠.这一时期的存在意味着,当睡眠发生时,某一活动开始出现.所有的陆生哺乳动物经检都呈现出这一时期,它与一种叫做静睡眠的非快速动眼期轮换出现,并有规律地循环.5 More recently, the field has made its greatest progress in characterizing the nature of sleep at the level of nerve cells (neurons) in the brain. In the past 20 years, scientists have mastered techniques for guiding fine microwires into various brain regions. Such wires produce no pain once implanted and have been used in humans as well as in a wide range of laboratory animals while they went about their normal activities, including sleep. These studies showed, as might be expected, that most brain neurons are at or near their maximum levels of activity while the subject is awake. But neuronal doings during sleep are surprisingly variable. Despite the similar posture and inattention to the environment that a sleeper shows during both REM and non-REM sleep, the brain behaves completely differently in the two states. 最近更多在大脑神经细胞水平上描述睡眠特性的领域取得了巨大的进展.过去20年,科学家已经掌握了控制精细微电极导入脑部神经各区域的技术.这种电极植入是无痛的,它已经使用在人类上,也广泛地使用在实验动物上,并不影响他们包括睡眠在内的一切正常活动.这些研究结果正如我们所预料的那样,当研究对象清醒的时候,其大部分脑神经在或接近最大的活跃状态.但是当睡眠时神经元的表现却惊人地不同.尽管睡眠者在快速动眼期和非快速动眼期睡眠的姿势和不注意的条件相同,脑神经在两种睡眠状态中的活动却完全不同.6 During non-REM sleep, cells in different brain regions do very different things. Most neurons in the brain stem, immediately above the spinal cord, reduce or stop firing, whereas most neurons in the cerebral cortex and adjacent forebrain regions reduce their activity by only a small amount. What changes most dramatically is their overall pattern of activity. During the awake state, a neuron more or less goes about its own individual business. During non-REM sleep, in contrast, adjacent cortical neurons fire synchronously, with a relatively low frequency rhythm. (Seemingly paradoxically, this synchronous electrical activity generates higher-voltage brain waves than waking does. Yet just as in an idling automobile, less energy is consumed when the brain idles in this way.) Breathing and heart rate tend to be quite regular during non-REM sleep, and reports of vivid dreams during this state are rare. 在非快速动眼期中,不同区域的脑神经细胞做不同的事情.在脊髓上面的大部分脑干细胞减少或停止活动,然而,大脑皮层和邻近的前脑区稍稍减少活动.最大的变化是整个大脑的活动形式.在清醒状态,每一个神经细胞或多或少地从事着自己的事情.在非快速动眼期却形成对比,邻近的皮层细胞以一种相对低频的节奏同步地活动.(看起来似乎自相矛盾,这种同步电活动产生比清醒时还要高压的脑电波.然而,正如空转的机器,用这种方式消耗很少的能量.)在非快速动眼期时,呼吸和心率趋于平静和有规律,此阶段,罕有梦境报道.7 A very small group of brain cells (perhaps totaling just 100,000 in humans) at the base of the forebrain is maximally active only during non-REM sleep. These cells have been called sleep-on neurons and appear to be responsible for inducing sleep. The precise signals that activate the sleep-on neurons are not yet completely understood, but increased body heat while an individual is awake clearly activates some of these cells, which may explain the drowsiness that so often accompanies a hot bath or a summer day at the beach. 在脑前区的基部有一小撮的脑细胞(大概总量为100000个)仅在非快速动眼期表现最活跃.这些细胞好像行使管理包括睡眠在内的职责,它们被称为睡眠性神经细胞.激发睡眠性神经细胞的精确信号目前仍然不完全了解,但是当个体清醒/体温升高时部分这些睡眠性神经细胞是明显地被激活,这种现象可以用来解释热水澡或夏日海滨浴后的睡意.8 On the other hand, brain activity during REM sleep resembles that during waking. Brain waves remain at low voltage, because neurons are behaving individually. And most brain cells in both the forebrain and brain stem regions are quite active, signaling other nerve cells at rates as high as - or higher than - rates seen in the waking state. The brains overall consumption of energy during REM sleep is also as high as while awake. The greatest neuronal activity accompanies the familiar twitches and eye motion that give REM sleep its name. Specialized cells located in the brain stem, called REM sleep on cells, become especially active during REM sleep and, in fact appear to be responsible for generating this state. 另一方面,快速动眼期的脑活动与清醒时的脑活动相似.脑电波仍然处于低电压状态,脑细胞仍然在各司其职.同时,脑前区和脑干区大部分细胞仍然十分活跃, 发出信号给其它神经细胞在比率上等于或高于清醒状态.在快速动眼期整个大脑的能量消耗也与清醒状态一样.在这个被称为快速动眼期的时段里,熟悉的抽搐和眼动伴随着最强烈的神经活动发生.9 Our most vivid dreams occur during REM sleep, and dreaming is accompanied by fr equent activation of the brains motor systems, which otherwise operate only during waking movement. Fortunately, most movement during REM sleep is inhibited by two complementary biochemical actions involving neurotransmitters, the chemicals that physically carry signals from one neuron to another at the synapse (the contact point between two neurons). The brain stops releasing neurotransmitters that would otherwise activate motoneurons, and it dispatches other neurotransmitters that actively shut down those motoneurons. These mechanisms, however, do not affect the motoneurons that control the muscles that move the eyes, allowing the rapid eye movements that give the REM sleep stage its name. 我们的梦境出现在快速动眼期, 梦境是随着大脑动力系统的频繁激活而产生的,大脑动力系统除在快速动眼期运转外,仅见于清醒状态.幸运的是,在快速动眼期很多运动都被两种互补的生化活动抑制住,这生化活动涉及神经传导物质,也就是一种在物理上能将信息在神经突触(就是联系两个神经细胞之间的节点)之间进行运载的化学物质.大脑停止释放神经传导物质,否则将激活运动神经元,和分配其它的神经传导物质及时地阻断那些运动神经元.然而,这种机制并不影响控制眼动的运动神经元的活动.10 REM sleep also profoundly affects brain systems that control the bodys internal organs. For example, heart rate and breathing become irregular during REM sleep, just as they are during active waking. Also, body temperature becomes less finely regulated and drifts, like that of a reptile, toward the environmental temperature. 快速动眼期也对大脑系统控制人体内脏器官产生深刻的影响.例如,在快速动眼期心率和呼吸如清醒时一样,变得不规律.体温也变得漂忽不稳定,像爬行动物一样趋向于环境的温度.11 This brief description of sleep at the neuronal levels is both accurate and as unsatisfying as being awakened before the completion of a good nights slumber. The tantalizing question persists: What is sleep for? 以上从神经元的水平对睡眠所进行的简述是精确的,但却是无法令人满意的,不满意之处在于,它如同没有完全睡够就被叫醒的那种感觉.那个撩人的问题还在: 为什么要睡眠?Section 3The Function of Sleep12 At a recent sleep conference, an attendee commented that the function of sleep remains a mystery. The chair of the session argued vehemently against that position - she did not, however, provide a concrete description of exactly why sleeps function was no longer mysterious. But based on the currently available evidence, I can put forth what many of us feel are some reasonable hypotheses. 在最近的一个关于睡眠的研讨会上,一个参会者发表评论说睡眠的功能仍是个秘密。而这个会议的主席却持相反意见,并准确的提出了为什么睡眠的功能不再是秘密的描述。但是基于目前可靠的证据,我提出一些大多数人认为是合理的假设。13 One approach to investigating the function of sleep is to see what physiological and behavioral changes result from a lack of it. More than a decade ago it was found that total sleep deprivation in rats leads to death. These animals show weight loss despite greatly increased food consumption, suggesting excessive heat loss. The animals die, for reasons yet to be explained, within 10 to 20 days, faster than if they were totally deprived of food but slept normally. 一个研究睡眠功能的方法是,看不睡眠的情况下生理和行为有什么变化。十多年前实验发现,如果没有睡眠,小鼠会死亡。这些被实验的动物表现出即使增加食物,体重减轻,并提示,过量的热散失。不睡眠,在10-20天动物会死,比不给食物但可睡眠的情况下死得更快,这死因仍待解释。14 In humans, a very rare degenerative brain disease called fatal familial Insomnia leads to death after several months. Whether the sleep loss itself is fatal or other aspects of the brain damage are to blame is not clear. Sleep deprivation studies in humans have found that sleepiness increases with even small reductions in nightly sleep times. Being sleepy while driving or during other activities that require continuous vigilance is as dangerous as consuming alcohol prior to those tasks. But existing evidence indicates that helping people to increase sleep time with long-term use of sleeping pills produces no clear-cut health benefit and may actually shorten life span. (About seven reported hours of sleep a night correlates with longer life spans in humans.) So inexorable is the drive to sleep that achieving total sleep deprivation requires repeated and intense stimulation. Researchers employing sleep deprivation to study sleep are therefore quickly confronted with the difficulty of distinguishing the effects of stress from those of sleep loss. Researchers also study the natural sleep habits of a variety of organisms. An important clue about the function of sleep is the huge variation in the amount that different species need. For example, the opossum sleeps for 18 hours a day, whereas the elephant gets by with only three or four. Closely related species that have genetic, physiological and behavioral similarities might also be expected to have similar sleep habits. Yet studies of laboratory, zoo and wild animals have revealed that sleep times are unrelated to the animals taxonomic classification: the range of sleep times of different primates extensively overlaps that of rodents, which overlaps that of carnivores. and so on across many orders of mammals. If evolutionary relatedness does not determine sleep time, then what does? 在人类中,极少有致命性家族性失眠症的脑疾病发生.睡眠缺失本身是否致命的或其他方面的脑损伤是罪魁祸首还不清楚。有关人类剥夺睡眠的研究发现,只需要减少很少的晚睡时间就可以使睡意增加.在困倦状态下驾车或做一些需要保持警醒的事情,那是如同酒后接受这些任务一样地危险.但现存的证据表明,用一些安眠的药物去帮助人们延长睡眠时间,没有明确的健康益处,事实上可能缩短寿命.(报道说,约每晚上7个小时的睡眠与长寿有关.)如此不可阻挡的睡眠内驱力使得取得实验所需的无眠总量需要反复地做和需要给予很强的激励.因而,研究者雇用无眠去研究睡眠很快就面临区分是压力效应还是睡眠缺失的困难.研究人员也研究各种生物体的自然睡眠习惯.关于睡眠功能的一个重要线索是不同生物种类需求不同,存在巨大的变数.例如,负鼠要睡每天18小时,而大象只需要3-4小时. 近缘种的遗传、生理和行为相似性可能也会有类似的睡眠习惯.然而,实验室动物园野外的动物研究揭示了睡眠时间与动物的分类学分类无关.不同灵长目动物的睡眠时间幅度与啮齿目的大量重叠, 啮齿目的睡眠时间又大量与肉食性动物等等,睡眠时间的重叠交错在哺乳动物中普通存在.15 The extraordinary answer is that size is the major determinant: bigger animals simply need less sleep. Elephants, giraffes and large primates (such as humans) require relatively little sleep; rats, cats, voles and other small animals spend most of their time sleeping. The reason is apparently related to the fact that small animals have higher metabolic rates and higher brain and body temperatures than large animals do, and metabolism is a messy business that generates free radicals - extremely reactive chemicals that damage and even kill cells. High metabolic rates thus lead to increased injury to cells and the nucleic acids, proteins and fats within them. 惊人的答案是,大小是睡眠长短主要的决定因素:大的动物仅需少许的睡眠,如大象长颈鹿大的灵长目动物(如人)需要相对少的睡眠;老鼠猫田鼠和其它小个体动物需要很多的睡眠时间.这原因显然与小个体动物比大个体动物有较高的代谢速率和较高的脑温及体温有关,新陈代谢是个复杂的机能,它能产生损害甚至杀死体内细胞,引起极端反应的化学物质自由基. 因此,高的代谢速率就会加大对体内细胞和核酸蛋白质脂肪的损害.16 Free-radical damage in many body tissues can be dealt with by replacing compromised cells with new ones, produced by cell division: however, most brain regions do not produce significant numbers of new brain cells after birth. The lower metabolic rate and brain temperature occurring during non-REM sleep seem to provide an opportunity to deal with the damage done during waking. For example, enzymes may more efficiently repair cells during periods of inactivity. Or old enzymes, themselves altered by free radicals, may be replaced by newly synthesized ones that are structurally sound. 自由基损害的身体组织可以通过产生新细胞的方式来补偿,新细胞的产生需要细胞分裂,然而,大脑大部分区域在出生后不能再产生有效数量的新脑细胞.低速率的代谢和低脑温在非快速动眼期出现看来是提供应对清醒状态下损害的一种条件.例如, 酶在休眠状态可以高效修复受损细胞.或者老酶自己被自由基改变,被结构完整的新合成的酶取代.17 Last year my group at the University of California at Los Angeles observed what we believe to be the first evidence for brain cell damage in rats, occurring as a direct result of sleep deprivation. This finding supports the idea that non-REM sleep wards off metabolic harm. 去年我的研究小组在旧金山加利佛尼严大学首次在小鼠中观察到由睡眠缺失引起的大脑细胞受损的证据.这一发现支持了非快速动眼期是避开代射损害的观点.18 REM sleep, however, is the proverbial riddle wrapped in a mystery inside an enigma. The cell-repair hypothesis could explain non-REM sleep, but it fails to account for REM sleep. After all, downtime repair cannot be taking place in most brain cells during REM sleep, when these cells are at least as active as during waking. But a specific group of brain cells that goes against this trend is of special interest in the search for a purpose of REM sleep. 众所周知,快速动眼期是一个被包裹在神秘秘团之中的秘语.细胞修复假说能对非快速动眼期进行解释,但却不能对快速动眼期进行解释.毕竟,当大脑大部分细胞处在相当于清醒时最低活跃程度的快速动眼期时,停机修复是不可能发生的.但是,一群与不同于这种趋势的特殊细胞成为研究快速动眼期功能的特别兴趣点.19 Recall that the release of some neurotransmitters ceases during REM sleep, thereby disabling body movement and reducing awareness of the environment. The key neurotransmitters affected are termed monoamines, because they each contain a chemical entity called an amine group. Brain cells that make these monoamines are maximally and continuously active in waking. But Dennis McGinty and Ronald Harper of D.C.L.A. discovered in 1973 that these cells stop discharging completely during REM sleep. 回想起在快速动眼期神经传导物质的释放终止,从而使身体运动和对周遭感觉失能.这关键起作用的神经传导物质叫做一元胺(因为它包含着一个叫做胺的化学基团).制造一元按的大脑细胞在清醒状态下是最大限度地和持续地活跃.可是, D.C.L.A的丹尼斯麦金蒂和罗纳德哈伯在1973年发现这些细胞在快速动眼期完全停止活动.20 In 1988 Michael Rogawski of the National Institutes of Health and I hypothesized that the cessation of neurotransmitter release is vital for the proper function of these neurons and of their receptors (the molecules on recipient cells that relay neurotransmitters signals in that cell). Various studies indicate that constant release of monoamines can desensitize the neurotransmitters receptors. The interruption of monoamine release during REM sleep thus may allow the receptor systems to rest and regain full sensitivity. And this restored sensitivity may be crucial during waking for mood regulation, which depends on the efficient collaboration of neurotransmitters and their receptors. 1988年国家卫生研究院的迈克尔.罗格斯奇和我假设,神经递质释放的终止是那些神经细胞及其受体(那些在受体细胞上传递神经递质信号的分子)极其重要的特有功能.多种研究表明,恒定地释放一元胺能使神经递质的受体失灵.在快速动眼期终止一元胺的释放因而可以允许受体系统”休息”,以致重获灵敏.恢复敏感性可能对清醒时的正常情绪是很重要的,它需要依靠神经递质及其受体的有效协调.Section 4Other Possibilities21 What else might REM sleep do? Researchers such as Frederick Snyder and Thomas Wehr of the National Institutes of Health and Robert Vertes of Florida Atlantic university have proposed that the elevated activity during REM sleep of brain cells that are not involved in monoamine production enables mammals to be more prepared than reptiles to cope with dangerous surroundings: When waking in a cold environment, reptiles are sluggish and require an external heat source to become active and responsive. But even though mammals do not thermoregulate during REM sleep, the intense neuronal activity during this phase can raise brain metabolic rate, helping mammals to monitor and react more quickly to a given situation on waking. The observation that humans are much more alert when awakened during REM sleep than during non-REM periods supports this idea. 快速动眼期还有别的功能?研究人员象弗雷德里格.斯尼特和国家卫生研究院的托马斯.威尔斯、佛罗里达大西洋大学的罗伯特.韦尔泰次曾提议大脑细胞在快速动眼期活力增强与一元胺物质无关,它是使哺乳动物较爬行动物能有更充分的准备去应付危险的环境:在寒冷的环境里,清醒着的爬行动物变得迟纯,需要外来的热源使自己变得活力和敏捷.即使哺乳动物在快速动眼期不调节体温, 但在这一阶段紧张的神经活动能使大脑代谢率提高,以使哺乳动物在清醒时对既定的环境进行更快地监控和及时地反应.22 Sleep deprivation studies indicate, however, that REM sleep must do more than prime the brain for waking experience. These studies show that animals made to go without REM sleep will undergo more than the usual amount when they are finally given the opportunity. They apparently seek to make up the debt - yet another clue that REM sleep is important. 然而,剥夺睡眠的研究表明,快速动眼期所做事情一定比大脑基本清醒状态下所经历的事多.这些研究显示, 动物如果没有快速动眼期那么将承受比最终获得睡眠时更多的付出.快速动眼期显然是为了寻求弥补”债务”,这一线索也是很重要的.23 Old ideas that REM sleep deprivation led to insanity have been convincingly disproved (although studies show that depriving someone of sleep, for example by prodding him or her awake repeatedly, can definitely caus

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