Chapter 11 - Wakefulness Sleep PDF

Wakefulness and Sleep Chapter 8 A nyone deprived of sleep suffers. But if life evolved on another planet...

Wakefulness and Sleep Chapter 8 A nyone deprived of sleep suffers. But if life evolved on another planet with different conditions, could animals evolve life without a need for sleep? Imagine a planet that doesn’t rotate on its axis. Some animals evolve Chapter Outline Module 8.1 Rhythms of Waking and Sleeping Endogenous Rhythms Setting and Resetting the Biological Clock adaptations to live in the light area, others in the dark area, and still others in Mechanisms of the Biological Clock the twilight zone separating light from dark. There would be no need for any In Closing: Sleep–Wake Cycles Module 8.2 animal to alternate active periods with inactive periods on any fixed schedule Stages of Sleep and Brain Mechanisms Sleep and Other Interruptions of and perhaps no need for prolonged inactive periods. If you were the astronaut Consciousness who discovered these sleepless animals, you might be surprised. The Stages of Sleep Paradoxical or REM Sleep Now imagine that astronauts from that planet set out on their first voyage Brain Mechanisms of Wakefulness, Arousal, and Sleep to Earth. Imagine their surprise to discover animals like us with long inactive Brain Activity in REM Sleep Sleep Disorders periods resembling death. To someone who hadn’t seen sleep before, it would In Closing: Stages of Sleep Module 8.3 seem mysterious indeed. For the purposes of this chapter, let’s adopt their Why Sleep? Why REM? Why Dreams? perspective and ask why animals as active as we are spend a third of our lives Functions of Sleep Functions of REM Sleep doing so little. Biological Perspectives on Dreaming In Closing: Our Limited Self-Understanding Learning Objectives After studying this chapter, you should be able to: 1. Define and describe endogenous rhythms. 2. Explain the mechanisms that set and reset the biological clock. 3. List and characterize the stages of sleep. 4. Describe the brain mechanisms of waking and sleeping. 5. Discuss several consequences of thinking of sleep as a localized phenomenon. 6. List several sleep disorders with their causes. 7. Evaluate possible explanations of the func- tions of sleep. 8. Describe possible explanations of dreaming. Opposite: Sleep is an important part of life for nearly all animals. (Hoberman Collection/Getty Images)   257 Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. WCN 02-200-203 Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  Module 8.1 Rhythms of Waking and Sleeping Y ou are probably not amazed to learn that your body spon- taneously generates its own rhythm of wakefulness and sleep. Psychologists of an earlier era strongly resisted that sleep all night—as most college students do, sooner or later—you feel sleepier and sleepier as the night goes on, but as morning arrives, you feel more alert, not less. Especially idea. When radical behaviorism dominated experimental psy- in the posterior areas of the cerebral cortex, activity corre- chology during the mid-1900s, many psychologists believed lates mainly with your circadian rhythm, and only second- that every behavior could be traced to external stimuli. There- arily with how long you have been awake (Muto et al., 2016). fore, they believed, alternation between wakefulness and Figure 8.1 represents the activity of a flying squirrel kept sleep must depend on something in the outside world, such in total darkness for 25 days. Each horizontal line represents as changes in light or temperature. Research as early as that one 24-hour day. A thickening in the line represents a period of Curt Richter (1922) implied that the body generates its own of activity. Even in this unchanging environment, the animal cycles of activity and inactivity, but it took decades of research generates a consistent rhythm of activity and sleep. Depend- to convince the skeptics. The idea of self-generated rhythms ing on the individual and the details of the procedure, the self- was a major step toward viewing animals as active producers generated cycle may be slightly shorter than 24 hours, as in of behaviors. Figure 8.1, or slightly longer (Carpenter & Grossberg, 1984). Endogenous Rhythms Waking period starts earlier each day than the last. An animal that produced its behavior entirely in response to Waking period current stimuli would be at a serious disadvantage. Animals 1 often need to anticipate changes in the environment. For ex- ample, migratory birds start flying toward their winter homes 5 Sleep period starts before their summer territory becomes too cold. A small bird earlier each day Days of experiment that waited for the first frost would probably die. Similarly, than the last. squirrels begin storing nuts and putting on extra layers of fat 10 in preparation for winter long before food becomes scarce. Animals’ readiness for a change in seasons comes partly 15 from internal mechanisms. Changes in the light–dark pattern of the day tell a migratory bird when to fly south for the 20 winter, but what tells it when to fly back north? In the tropics, the temperature and amount of daylight are nearly the same throughout the year. Nevertheless, migratory birds fly north 25 at the right time. Even if they are kept in a cage with no clues to the season, they become restless in the spring, and if they are noon 6 pm midnight 6 am noon released, they fly north (Gwinner, 1986). Evidently, birds gen- Time of day in hours erate a rhythm that prepares them for seasonal changes. We Figure 8.1 Activity record of a flying squirrel kept in constant refer to that rhythm as an endogenous circannual rhythm. darkness (Endogenous means “generated from within.” Circannual The thickened segments indicate periods of activity as measured by a comes from the Latin words circum, for “about,” and annum, running wheel. Note that this free-running activity cycle lasts slightly less for “year.”) than 24 hours. Animals also produce endogenous circadian ­rhythms­ (Source: From “Phase control of activity in a rodent,” by P. J. DeCoursey, 1960, Cold that last about a day. (Circadian comes from the Latin Spring Harbor Symposia on Quantitative Biology, 25, pp. 49–55. Reprinted by permission of Cold Spring Harbor and P. J. DeCoursey.) circum, for “about,” and dies, for “day.”) If you go without 258   Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. WCN 02-200-203 Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  8.1 Rhythms of Waking and Sleeping   259 Humans also generate 24-hour wake–sleep rhythms, Regardless of whether people started this procedure at which we can modify only a little. If we ever send astro- 10 a.m. or 5 p.m., most reported their most pleasant mood nauts to Mars, they will have to adjust to the Martian day, around 5 p.m. and their least pleasant mood at around which lasts about 24 hours and 39 minutes of Earth time. 5 a.m. (Murray et al., 2009). These results suggest a biologi- Engineers who were monitoring the Phoenix robot mission cally driven circadian rhythm in our emotional well-being on Mars had to live on the Martian schedule, starting work (see Figure 8.3). 39 minutes later each day. Most (13 15 who were studied) managed to synchronize their biological rhythms to the Martian schedule, although they did not sleep as much as STOP & CHECK usual, and some of them suffered a loss of alertness (Barger et al., 2012). 1. What evidence indicates that humans have an internal Our circadian rhythm does not easily adjust to more biological clock? severe departures from a 24-hour schedule. Naval person- ANSWER about a 24-hour basis. nel on submarines are cut off from sunlight for months at a that schedule and instead become wakeful and sleepy on time, living under faint artificial light. In many cases, they dark schedule much different from 24 hours fail to follow live on a schedule of 6 hours of work, 6 hours of recreation, 1. People who have lived in an environment with a light– and 6 hours of sleep. Even though they try to sleep on this 18-hour schedule, their bodies generate rhythms of alertness and body chemistry that average about 24.3 to 24.4 hours (Kelly et al., 1999). Circadian rhythms affect much more than just waking Setting and Resetting and sleeping. We have circadian rhythms in our eating and drinking, urination, hormone secretion, metabolism, sensi- the Biological Clock tivity to drugs, and other variables. For example, although Our circadian rhythms generate a period close to 24 hours, we ordinarily think of human body temperature as 37°C, but they are not perfect. We readjust our internal workings our temperature fluctuates over the course of a day from daily to stay in phase with the world. Sometimes, we misadjust a low near 36.7°C during the night to almost 37.2°C in late them. On weekends, when most of us are freer to set our own afternoon (see Figure 8.2). We also have circadian rhythms schedules, we expose ourselves to lights, noises, and activity in mood. In one study, young adults recorded their mood at night and then awaken late the next morning. By Monday throughout the day. Most showed increases in positive morning, when the clock on your table indicates 7 a.m., mood (happiness) from waking until late afternoon, and your biological clock may say 5 a.m., and you stagger off to then a slight decline until bedtime. In a follow-up study, the work or school without much pep (Moore-Ede, Czeisler, & same investigators kept young adults awake for 30 consecu- Richardson, 1983). tive hours, starting at either 10 a.m. or 5 p.m., in a labora- Although circadian rhythms persist without light, your tory setting with constant levels of light and temperature. rhythm is not perfect. Unless something resets it from time to time, it would gradually drift away from the correct time. The stimulus that resets the circadian rhythm is referred to by the 37.2 98.9 German term zeitgeber (TSITE-gay-ber), meaning “time-giver.” 98.8 Light is by far the dominant zeitgeber for land animals (Rusak & 37.1 Rectal temperature (°C) Rectal temperature (°F) 98.7 Zucker, 1979), whereas the tides are important for some marine 37.0 98.6 animals. In addition to light, other zeitgebers include exercise 98.5 (Eastman, Hoese, Youngstedt, & Liu, 1995), arousal of any kind 36.9 98.4 (Gritton, Sutton, Martinez, Sarter, & Lee, 2009), meals, and 98.3 the temperature of the environment (Refinetti, 2000). Social 36.8 stimuli—that is, the effects of other people—are ineffective as 98.2 98.1 zeitgebers, unless they induce exercise or other vigorous ac- 36.7 98.0 tivity (Mistlberger & Skene, 2004). Although these additional 36.6 97.9 zeitgebers modify the effects of light, they have only weak ef- –12 –10 –8 –6 –4 –2 0 2 4 6 8 fects on their own. For example, people who are working in Hours from sleep onset Antarctica during the constant darkness of an Antarctic winter Figure 8.2 Mean rectal temperatures for nine adults try to maintain a 24-hour rhythm, but they drift away from it. Body temperature reaches its low for the day about 2 hours after sleep Different people generate slightly different rhythms, until they onset; it reaches its peak about 6 hours before sleep onset. find it more and more difficult to work together (Kennaway & (Source: From “Sleep-onset insomniacs have delayed temperature rhythms,” by Van Dorp, 1991). Astronauts in orbit face a special problem: As M. Morris, L. Lack, and D. Dawson, 1990, Sleep, 13, pp. 1–14. Reprinted by permission.) they orbit the Earth, a 45-minute period of daylight alternates Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. WCN 02-200-203 Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  260  Chapter 8 Wakefulness and Sleep 2.5 Particularly impressive evidence for the Reports of positive mood, relative 2 importance of sunlight comes from a study in 1.5 Germany. Sunrise occurs at the eastern end to an average of zero 1 of Germany about half an hour earlier than at the western end, even though all people 0.5 set their clocks to the same time. Researchers 0 asked adults for their preferred times of awak- –0.5 ening and going to sleep and determined for –1 each person the midpoint of those values. For –1.5 example, if on weekends and holidays you pre- –2 fer to go to bed at 12:30 a.m. and awaken at –2.5 8:30 a.m., your sleep midpoint is 4:30 a.m.............. M M M Figure 8.4 shows the results. People at the P.M P.M P.M P.M P.M P.M M M M P.M A. A. A. A. A. A. 1 3 5 7 9 11 1 1 3 5 7 9 11 Time (hr) eastern edge have a sleep midpoint about 30 minutes earlier than those at the west, cor- 2 responding to the fact that the sun rises earlier Reports of positive mood, relative 1.5 at the eastern edge (Roenneberg, Kumar, & 1 Merrow, 2007). Other researchers reported to an average of zero 0.5 similar results for Turkey and South Africa (Masal et al., 2015; Shawa & Roden, 2016). 0 What about blind people, who need to –0.5 set their circadian rhythms by zeitgebers –1 other than light? The results vary. Some –1.5 do set their circadian rhythms by noise, –2 temperature, meals, and activity. However, others who are not sufficiently sensitive to –2.5 these secondary zeitgebers produce circa-............. P.M P.M M M M M M P.M P.M P.M P.M P.M P.M A. A. A. A. A. dian rhythms that are a little longer than 24 7 11 1 3 5 7 1 3 5 9 11 9 9 Time (hr) hours. When their cycles are in phase with Figure 8.3 Reported positive mood over time During 30 hours in an unchanging laboratory environment, the average young adult reported the clock, all is well, but when they drift out most pleasant mood in the late afternoon or early evening, and the least pleasant mood of phase, they experience insomnia at night around 5 to 7 a.m. The pattern was similar for those who started the procedure in the and sleepiness during the day (Sack & Lewy, morning (above) or in the evening (below). 2001). More than half of all blind people (Source: From “Nature’s clocks and human mood: The circadian system modulates reward motivation,” by report frequent sleep problems (Warman G. Murray, C. L. Nicholas, J. Kleiman, R. Dwyer, M. J. Carrington, N. B. Allen, et al., 2009, Emotion, 9, pp. 705–716.) et al., 2011). 4.8 with 45 minutes of darkness. If they retreat from the flight deck to elsewhere in the spacecraft, they have constant dim light. As 4.6 Midpoint of the a result, they are not fully alert during their wakeful periods or night’s sleep deeply asleep during rest periods (Dijk et al., 2001). On long as- 4.4 signments, many of them experience depression and impaired performance (Mallis & DeRoshia, 2005). 4.2 Even when we try to set our wake–sleep cycles by the 4.0 clock, sunlight has its influence. Consider what happens when we shift to daylight saving time in spring. You set your clock 3.8 to an hour later, and when it shows your usual bedtime, you West East dutifully go to bed, even though it seems an hour too early. The next morning, when the clock says it is 7 a.m. and time Figure 8.4 Sun time competes with social time On days when people have no obligation to awaken at a particular time, they to get ready for work, your brain registers 6 a.m. Most people awaken about half an hour earlier at the eastern edge of Germany than at the remain ill rested for days after the shift to daylight saving time. western edge. Points along the y axis represent the midpoint between the The adjustment is especially difficult for people who were preferred bedtime and the preferred waking time. Data are for people living in already sleep deprived, including most college students towns and cities with populations less than 300,000. (Lahti et al., 2006; Monk & Aplin, 1980). In fall, when daylight (Source: From “The human circadian clock entrains to sun time,” by T. Roenneberg, C. J. saving time ends, some people have sleep problems then, Kumar, and M. Merrow, 2007, Current Biology, 17, pp. R44–R45. Reprinted by permission of the Copyright Clearance Center.) too (Harrison, 2013). Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. WCN 02-200-203 Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  8.1 Rhythms of Waking and Sleeping   261 STOP & CHECK could be air travel itself. A good control group would have been flight attendants who flew long north–south routes. 2. Why do people at the eastern edge of a time zone awaken earlier than those at the western edge on their weekends and holidays? Shift Work People who sleep irregularly—such as pilots, medical interns, ANSWER and shift workers in factories—find that their duration of sleep for their work schedule. schedules even when people follow the same clock time western edge. Evidently, the sun controls waking–sleeping depends on when they go to sleep. When they have to sleep in 2. The sun rises earlier at the eastern edge than at the the morning or early afternoon, they sleep only briefly, even if they have been awake for many hours (Frese & Harwich, 1984; Winfree, 1983). People who have done shift work for years tend to perform worse than average on cognitive tests, although be- cause the measures are correlational, we cannot be sure of cause Jet Lag and effect (Marquié, Tucker, Folkard, Gentil, & Ansiau, 2015). A disruption of circadian rhythms due to crossing time zones People who work on a night shift, such as midnight to is known as jet lag. Travelers complain of sleepiness during 8 a.m., sleep during the day. At least they try to. Even after the day, sleeplessness at night, depression, and impaired con- months or years on such a schedule, many workers adjust in- centration. All these problems stem from the mismatch be- completely. They continue to feel groggy on the job, they sleep tween internal circadian clock and external time (Haimov & poorly during the day, and their body temperature continues Arendt, 1999). Most people find it easier to adjust to crossing to peak when they are sleeping in the day instead of while time zones going west than east. Going west, we stay awake they are working at night. In general, night-shift workers have later at night and then awaken late the next morning, already more accidents than day-shift workers. partly adjusted to the new schedule. We phase-delay our cir- People who work at night have great difficulty adjusting cadian rhythms. Going east, we phase-advance to sleep earlier their circadian rhythm, because most buildings use artificial and awaken earlier (see Figure 8.5). Most people find it dif- lighting in the range of 150 to 180 lux, which is only moderately ficult to go to sleep before their body’s usual time and difficult effective in resetting the rhythm (Boivin, Duffy, Kronauer, & to wake up early the next day. Czeisler, 1996). People adjust best to night work if they sleep in a Adjusting to jet lag is often stressful. Stress elevates blood very dark room during the day and work under very bright lights levels of the adrenal hormone cortisol, and many studies have at night, comparable to the noonday sun (Czeisler et al., 1990). shown that prolonged elevations of cortisol damage neurons Short-wavelength (bluish) light helps to reset the circadian in the hippocampus, a brain area important for memory. One rhythm better than long-wavelength light does (Czeisler, 2013). study examined flight attendants who had spent the previous 5 years making flights across seven or more time zones—such as Chicago to Italy—with mostly short breaks (fewer than Morning People and Evening People 6 days) between trips. On the average, the flight attendants had Circadian rhythms differ among individuals. Some people smaller than average volumes of the hippocampus and sur- (“morning people,” or “larks”) awaken early, reach their peak rounding structures, and they showed memory impairments of productivity early, and become less alert later in the day. (Cho, 2001). These results suggest a danger from repeated ad- Others (“evening people,” or “owls”) warm up more slowly, justments of the circadian rhythm, although the problem here both literally and figuratively, reaching their peak in the late (a) Leave New York at 7 P.M. (b) Arrive in London at 7 A.M., which is 2 A.M. in New York Figure 8.5 Jet lag Eastern time is later than western time. People who travel five time zones east fall asleep on the plane and then must awaken when it is morning at their destination but night back home. Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. WCN 02-200-203 Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. 262  Chapter 8 Wakefulness and Sleep afternoon or evening. They tolerate staying up all night bet- In similar societies after gaining electric lights, people stay awake ter than morning people do (Taillard, Philip, Coste, Sagaspe, later and get less sleep (de la Iglesia et al., 2015; Yetish et al., & Bioulac, 2003). Among shift workers, morning people are 2015). People who live in a big city, surrounded by bright lights, most impaired when working the night shift and evening peo- are more likely to stay up late than are people in rural areas. ple are most impaired when working the morning shift (Juda, The tendency for most young people to be evening types Vetter, & Roenneberg, 2013). Many people are, of course, in- causes problems. In the United States and many other countries, termediate between the two extremes. high school classes start at 8:00 a.m. or earlier. Most teenagers A convenient way to classify people is to ask, “On holidays are at least a bit drowsy at that time, some more than others. and vacations when you have no obligations, what time is the Those who are strongly evening types tend to get lower than middle of your sleep?” For example, if you sleep from 1 a.m. un- average test scores, especially in their morning classes, even if til 9 a.m. on those days, your middle is 5 a.m. As Figure 8.6 they have average or above-average intelligence (Preckel, Lipn- shows, people differ by age. As a child, you almost certainly evich, Anastasiya, Schneider, & Roberts, 2011; Preckel et al., went to bed early and woke up early. As you entered adoles- 2013; van der Vinne et al., 2015). Possibly as a result of school cence, you started staying up later and waking up later, when frustration, or perhaps just as a result of staying up late, they you had the opportunity. The mean preferred time of going to are more likely than others to use alcohol, overeat, and engage sleep gets later and later until about age 20 and then gradually in other risky behaviors (Hasler & Clark, 2013; Roenneberg, reverses (Roenneberg et al., 2004). The tendency to stay up later Allebrandt, Merrow, & Vetter, 2012). Even beyond the teenage and awaken later during adolescence occurs in every culture years, morning people report being happier than evening peo- that researchers have studied throughout the world (Gradisar, ple, on average, possibly because their biological rhythms are Gardner, & Dohnt, 2011). The same trend also occurs in rats, more in tune with their 9-to-5 work schedule (Biss & Hasher, monkeys, and other species (Hagenauer & Lee, 2012; Wino- 2012). The morning type versus evening type distinction affects cur & Hasher, 1999, 2004), apparently resulting from increased other aspects of behavior also. One study found that morning levels of sex hormones (Hagenauer & Lee, 2012; Randler et al., type people tend to be more moral and honest in the morning, 2012). From a functional standpoint, we can only speculate as whereas evening type people tend to be more moral and honest to why staying up late and waking up late might be more advan- in the evening (Gunia, Barnes, & Sah, 2014). tageous for adolescents than for children or adults. So, being a morning person or an evening person depends partly on age. It also depends on genetics and several environ- Mechanisms of the Biological Clock mental factors, including artificial light. In low-tech societies How does the body generate a circadian rhythm? Curt Rich- without electric lights, people go to sleep about three hours after ter (1967) introduced the concept that the brain generates its sunset, seldom awaken during the night, and wake up at sunrise. own rhythms—a biological clock—and he reported that the Males 5 Time of the middle of sleep on Females days without obligations 4 Figure 8.6 Age differences in circa- dian rhythms People reported the time of the middle of their sleep, such as 3 a.m. or 5 a.m., on days 3 when they had no obligations. (Source: Reprinted from “A marker for the end of adolescence,” by T. Roenneberg et al., Current Biology, 14, pp. R1038–R1039, Figure 1, copyright 10 20 30 40 50 60 2004, with permission from Elsevier.) Age (years) Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. WCN 02-200-203 Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  8.1 Rhythms of Waking and Sleeping   263 biological clock is insensitive to most forms of interference. The Suprachiasmatic Nucleus (SCN) Blind or deaf animals generate circadian rhythms, although they slowly drift out of phase with the external world. The circadian Although cells throughout the body generate circadian rhythm remains surprisingly steady despite food or water de- rhythms, the main driver of rhythms for sleep and body tem- privation, X-rays, tranquilizers, alcohol, anesthesia, lack of oxy- perature is the suprachiasmatic (soo-pruh-kie-as-MAT-ik) gen, most kinds of brain damage, or the removal of endocrine nucleus, or SCN, a part of the hypothalamus (Refinetti & organs. Even an hour or more of induced hibernation often Menaker, 1992). It gets its name from its location just above fails to reset the biological clock (Gibbs, 1983; Richter, 1975). (“supra”) the optic chiasm (see Figure 8.7). After damage to Evidently, the biological clock is a hardy, robust mechanism. the SCN, the body’s rhythms become erratic. The SCN generates circadian rhythms itself in a geneti- cally controlled manner. If SCN neurons are disconnected from the rest of the brain or removed from the body and maintained in tissue culture, they continue to produce a circadian rhythm of action potentials (Earnest, Liang, Ratcliff, & Cassone, 1999; Inouye & Kawamura, 1979). Even a single isolated SCN cell can Massachusetts at Amherst maintain a circadian rhythm, although interactions among cells Elliott Blass/University of Curt P. Richter sharpen the accuracy of the rhythm (Long, Jutras, Connors, & (1894–1988) Burwell, 2005; Yamaguchi et al., 2003). I enjoy research more than eating. (Richter, A mutation in one gene causes hamsters’ SCN to produce personal communication) a 20-hour instead of 24-hour rhythm (Ralph & Menaker, 1988). Corpus callosum Thalamus Cerebral cortex Figure 8.7 The suprachias- Basal matic nucleus (SCN) of rats ganglia SCN and humans (a) (b) The SCN is at the base of the brain, as seen in these coronal sections through the plane of the anterior hypothalamus. Each Cerebral cortex rat was injected with radioac- tive 2-deoxyglucose, which is absorbed by the most active neurons. A high level of absorp- tion of this chemical produces a dark appearance on the slide. Note the greater activity in SCN neurons of a rat injected during the day (a), than in one injected at night (b). Pineal gland (Source: From “Suprachiasmatic Suprachiasmatic nucleus: Use of 14C-labeled deoxyglu- nucleus cose uptake as a functional marker,” by W. J. Schwartz and H. Gainer, 1977, Science, 197, pp. 1089–1091. Optic chiasm Reprinted by permission from AAAS/American Association for the Advancement of Science.) (c) A sagittal section through a Hypothalamus human brain showing the loca- tion of the SCN and the pineal (c) gland. Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. WCN 02-200-203 Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. 264  Chapter 8 Wakefulness and Sleep Researchers surgically removed the SCN from adult hamsters eyes are covered with folds of skin and fur. They are evolution- and transplanted SCN tissue from hamster fetuses into the arily adapted to spend most of their lives underground. They adults. When they transplanted SCN tissue from fetuses with have fewer than 900 optic nerve axons compared with 100,000 a 20-hour rhythm, the recipients produced a 20-hour rhythm. in hamsters. Even a bright flash of light evokes no startle re- When they transplanted tissue from fetuses with a 24-hour sponse and no measurable change in brain activity. Neverthe- rhythm, the recipients produced a 24-hour rhythm (Ralph, less, light resets their circadian rhythms, enabling them to be Foster, Davis, & Menaker, 1990). That is, the rhythm followed awake only at night (de Jong, Hendriks, Sanyal, & Nevo, 1990). the pace of the donors, not the recipients. Again, the results The surprising explanation is that the retinohypotha- show that the rhythms come from the SCN itself. lamic path to the SCN comes from a special population of retinal ganglion cells that have their own photopigment, called melanopsin, unlike the ones found in rods and cones STOP & CHECK (Hannibal, Hindersson, Knudsen, Georg, & Fahrenkrug, 2001; Lucas, Douglas, & Foster, 2001). These special ganglion cells 3. What evidence strongly indicates that the SCN produces the receive some input from rods and cones (Gooley et al., 2010; circadian rhythm itself? Güler et al., 2008), but even if they do not receive that input, the donor animals. they respond directly to light (Berson, Dunn, & Takao, 2002). ANSWER neurons, their circadian rhythm followed the pattern of These special ganglion cells are located mainly near the nose, body. Also, when hamsters received transplanted SCN from which they see toward the periphery (Visser, Beersma, & Daan, 1999). They respond to light slowly and turn off slowly if they are kept in cell culture isolated from the rest of the 3. SCN cells produce a circadian rhythm of activity even when the light ceases (Berson, Dunn, & Takao, 2002). There- fore, they respond to the overall average amount of light, not to instantaneous changes in light. The average intensity over How Light Resets the SCN a period of time is, of course, exactly the information the SCN needs to gauge the time of day. These ganglion cells respond Figure 8.7 shows the position of the SCN in the human brain, mainly to short-wavelength (blue) light. For that reason, ex- just above the optic chiasm. A small branch of the optic nerve, posure to television, video games, computers, and so forth, all known as the retinohypothalamic path, from the retina to the of which emit mostly short-wavelength light, tends to phase- SCN, alters the SCN’s settings. delay the circadian rhythm and make it difficult to fall asleep Most of the input to that path, however, does not come at the usual time (Czeisler, 2013). from normal retinal receptors. Mice with genetic defects that destroy nearly all their rods and cones nevertheless reset their biological clocks in synchrony with the light (Freedman et al., STOP & CHECK 1999; Lucas, Freedman, Muñoz, Garcia-Fernández, & Foster, 1999). Also, consider blind mole rats (see Figure 8.8), whose 4. How does light reset the biological clock? 5. People who are blind because of cortical damage can still syn- chronize their circadian rhythm to the local pattern of day and night. Why? messages to the SCN, resetting its rhythm. ANSWERS intact, melanopsin-containing ganglion cells can still send do not receive input from rods or cones. 5. If the retina is glion cells that respond to light by themselves, even if they axons comprising that path originate from special gan- path, conveys information about light to the SCN. The 4. A branch of the optic nerve, the retinohypothalamic The Biochemistry of the Circadian Rhythm The suprachiasmatic nucleus produces the circadian rhythm, but how? Research on production of the circadian rhythm began with insects. Studies on the fruit fly Drosophila found several genes responsible for a circadian rhythm (X. Liu et al., Figure 8.8 A blind mole rat 1992; Sehgal, Ousley, Yang, Chen, & Schotland, 1999). Two of Although blind mole rats are blind in other regards, they reset their circa- these genes, known as period (abbreviated PER) and timeless dian rhythms in response to light. (TIM), produce the proteins PER and TIM. The concentra- (Source: Courtesy of Eviatar Nevo) tion of these two proteins, which promote sleep and inactivity, Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. WCN 02-200-203 Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  8.1 Rhythms of Waking and Sleeping   265 Sunrise Sunset Sunrise Day Night Per and tim mRNA concentrations PER and TIM protein concentrations Wakefulness Sleep Wake Figure 8.9 Feedback between proteins and genes to control sleepiness In fruit flies (Drosophila), the concentrations of the mRNA levels for PER and TIM oscillate over a day, and so do the proteins that they produce. oscillates over a day, based on feedback interactions among STOP & CHECK neurons. Early in the morning, the messenger RNA levels re- sponsible for producing PER and TIM start at low concentra- 6. How do the proteins TIM and PER relate to sleepiness in tions. As they increase during the day, they increase synthesis Drosophila? of the proteins, but the process takes time, and so the protein declines toward morning. ANSWER concentrations lag hours behind, as shown in Figure 8.9. As the to inhibit the genes that produce them, so that their level PER and TIM protein concentrations increase, they feed back high levels at night, promoting sleep. They also feed back to inhibit the genes that produce the messenger RNA mole- the day and begin to increase toward evening. They reach cules. Thus, during the night, the PER and TIM concentrations 6. The proteins TIM and PER remain low during most of are high, but the messenger RNA concentrations are declin- ing (Nitabach & Taghert, 2008). By the next morning, PER and TIM protein levels are low, the flies awaken, and the cycle is ready to start again. Because the feedback cycle takes about 24 hours, the flies generate a circadian rhythm even in an un- Melatonin changing environment. However, in addition to the automatic The SCN regulates waking and sleeping by controlling activity feedback, light activates a chemical that breaks down the TIM levels in other brain areas, including the pineal gland (PIN-ee-al; protein, thereby increasing wakefulness and synchronizing the see Figure 8.7), an endocrine gland located just posterior to the internal clock to the external world (Ashmore & Sehgal, 2003). thalamus (Aston-Jones, Chen, Zhu, & Oshinsky, 2001; von Gall Why do we care about flies? The reason is that analyz- et al., 2002). The pineal gland releases the hormone melatonin. ing the mechanism in flies told researchers what to look for Melatonin is a widespread chemical, found in nearly all animals— in humans and other mammals. Mammals have three ver- sponges are the only known exception—as well as in plants and sions of the PER protein and several proteins closely related bacteria. In all cases, it is released mostly at night. In diurnal ani- to TIM and the others found in flies (Reick, Garcia, Dudley, & mals like humans, it increases sleepiness. In nocturnal animals, McKnight, 2001; Zheng et al., 1999). Mutations in the genes it increases wakefulness, even in such a remote example as the producing PER proteins lead to alterations of sleep schedules. larval form of a marine worm (Tosches, Bucher, Vopalensky, & People with certain PER mutations have been found to have a Arendt, 2014). People who have pineal gland tumors sometimes circadian rhythm shorter than 24 hours, as if they were mov- stay awake for days at a