Wednesday, May 25, 2005

Become An Early Riser....If You Can!

When your job, e.g., teaching school, forces you to become an early riser, it is easy in theory, but practice is everything I wrote before, a number of times, especially here.r

Wednesday, May 18, 2005

Development of Sleep

Infant Sleep: A Precursor to Adult Sleep? by Karl Karlsson, Mark Blumberg et al.

A central element of their hypothesis revolves around the nature of infant sleep and whether the neural mechanisms of infant sleep differ significantly from those of adult sleep. Infant rats, like the offspring of other “altricial” species (born naked, helpless, and blind), spend most of their time in what's now called active sleep, indicated by intermittent muscle twitching and low muscle tone (atonia)—behaviors characteristic of adult REM sleep. At issue is whether infant mechanisms are primitive, undifferentiated, and distinct from adult mechanisms or whether they contain elementary components that are integrated into the developing sleep system.

In a new study, Karl Karlsson, Mark Blumberg, and their colleagues tackle the technical difficulties involved in studying the tiny neonatal brain to investigate the neural activity associated with infant sleep states. The active sleep of week-old rats, they show, bears a striking resemblance to the conventional definitions of adult sleep. What's more, the neural mechanisms underlying the infant sleep state contain the primary components of adult sleep.
Altogether, the authors argue, these results show that sleep development elaborates on elementary components already in place soon after birth. If the neural mechanisms of infant and adult sleep were entirely different, then sleep might serve different purposes in infancy and adulthood. But the striking parallels outlined in this study suggest a developmental continuity between the two states. They also chart a course for future study that might even test Roffwarg's view that the neonatal brainstem primes the central nervous system for the sensory challenges that lie ahead—and could even be the stuff that dreams are made of.
Further review of this study is here: Functional Implications of Sleep Development by Jerome M. Siegel
Although frazzled new parents may beg to differ, infants do sleep more than adults. This sleep pattern is seen in a wide variety of mammalian species, with some obvious selective advantages. Sleep is a time of reduced body and brain metabolic rate [1,2], allowing energy conservation, particularly if a warm place is available, as can be provided by a compliant parent or sibling. The sleeping, quiescent infant is also less likely to attract predators and is easier to transport. At the earliest ages, infants who have not yet opened their eyes and whose cortex is not yet developed have limited learning opportunities from interactions with the outside world: another reason for reduced waking.

But sleep comes in many forms. Evolutionary arguments may make sense for slow-wave deep sleep patterns at birth that are associated with a general shutdown of the brain, but may not provide such an obvious explanation for the relative predominance of rapid eye movement (REM) sleep. For example, in human neonates REM sleep constitutes approximately eight hours per day, or 50% of the total sleep time, whereas human adults devote less than two hours per day, or 20% of their seven to eight hours of sleep time, to REM sleep [3]. REM sleep is characterized by high brain metabolic and neuronal activity rates [4], reduced muscle tone, irregular and relatively automatic respiration uncoupled from its usual regulatory mechanisms [5], and diminished thermoregulation [6]. These properties seem maladaptive, which suggests that there must be some compensatory survival benefit for REM sleep to have persisted. Could REM sleep play a particularly important role in development?

Interesting evidence for this hypothesis has come from studying the effects of REM sleep deprivation on the development of the visual system. It is known that the occlusion of one eye during the maturation of visual connections that occurs after birth causes the open eye to acquire more central connections than the closed eye. This disproportionate representation seems to result from a difference of activity in the optic nerve between the open eye and closed eye [7]. Although early ideas that REM sleep was necessary for brain plasticity might suggest that REM sleep deprivation would prevent this reorganization, just the reverse occurs. REM sleep deprivation accelerates the shift of connections to favor the open eye [8,9]. Rather than facilitating change [10], REM sleep may therefore be a source of endogenous activity that tends to prevent altered sensory stimulation from causing abnormal connections to form. REM sleep may prevent the programmed cell death and the pruning of connections that occurs when critical synapses are not stimulated.

Another possible role for neonatal REM sleep might be in thermoregulation of the growing brain. It is known that nonREM sleep tends to cool the brain, reducing its thermoregulatory set point [11]. In contrast, REM sleep tends to heat certain brain regions [12]. The nonREM–REM alternation comprises a thermoregulatory oscillation.

It is often assumed that the amount of time spent in different sleep states is determined by processes controlled by the cerebral cortex. The emphasis on the cortical role in sleep may result more from the technical ease of recording electroencephalograms from the cortex than from persuasive functional evidence. At birth, cortical metabolism and neuronal firing are minimal [13], yet this is the time of greatest sleep. In adults, damage to the cortex produces little or no change in sleep, indicating that the signal for sleep does not originate in or at least does not require the cortex [14]. Animals with proportionally larger cortices do not have more REM or nonREM sleep time than animals with relatively little cortex [15]. The effects of long-term sleep deprivation have been shown to be largely autonomic in nature, including elevated body temperature, skin lesions, and increased food intake [16]. Such effects cannot be duplicated by any cortical lesions. However, many of these symptoms appear to be consistent with hypothalamic dysfunction [17,18].

Evolutionary evidence also suggests that the cortex may be a relatively recent participant in REM sleep. Plesiomorphic (primitive) mammals such as the egg-laying echidna and platypus have large amounts of REM-sleep-like activity in brainstem structures at birth [19,20]. The brainstem is the key region for REM sleep generation, being both necessary and sufficient for its occurrence [4]. However, the cortex of these animals scarcely changes activity during these states, showing slow-wave patterns during the REM sleep state. In this respect the sleep of placental mammals may represent ontogeny recapitulating phylogeny, since a reduction in electroencephalogram power is a late-developing component of REM sleep.

A prominent feature of REM sleep is the rapid eye movements and associated twitches that define the state. These are particularly marked and vigorous in neonates. It has been shown that twitches with some resemblance to REM sleep activity are present in the isolated spinal cord of neonates and diminish in the transected cord of older animals [13]. This has suggested to some that a primal phasic activity of the central nervous system transforms postnatally over an extended time period into the very different brainstem-generated pattern seen in adults. But in this issue of PLoS Biology, Karlsson et al. [21] show that this is not the case. In a set of technically demanding experiments, they demonstrate a remarkable similarity between sleep control mechanisms in the one-week-old rat and those in the adult cat, and by implication throughout the mammalian line.

By severing the connections to and from the forebrain (cerebral cortex and associated structures), Karlsson et al. were able to study sleep-related activity in the midbrain and brainstem. They described the rat homologs of the medullary neurons that induce the atonia seen in sleeping adult cats and narcoleptic dogs [22,23,24] (Figure 1). More rostrally, they identified neural activity in the region of the locus coeruleus that facilitates movement and report contrasting inhibitory activity in the adjacent subcoeruleus region, again paralleling studies in the cat [25,26,27]. They also found cells that appear to generate or at least contribute to the twitches of REM sleep.
The similarities to the adult cat's REM sleep control mechanisms are so striking that what becomes interesting are the small differences that are reported. The locus coeruleus REM “sleep-off cells,” which are active in waking, reduce activity in nonREM sleep, and cease activity in REM sleep, appear to not have long-duration waveforms in the neonatal animals examined by Karlsson et al., unlike the case of the adult rat and cat [28,29]. Another difference is the apparent absence of the cessation of dorsal raphe (serotonin) unit discharge in REM sleep. Although the authors speculate that this is due to the absence of forebrain connections in their experimental preparation, it has been shown that forebrain mechanisms are not necessary for this cessation of raphe activity in adult cats [30]. However, identification of the narrow dorsal raphe nucleus is difficult even in adult cats, and it is certainly possible that these neurons were overlooked in the neonatal rat.

The upshot of these findings is a picture of a largely mature REM sleep generator mechanism at birth. The developmental progression of REM sleep signs, particularly the reduction in sleep duration and the development of the characteristic reduction in electroencephalogram voltage to a waking-like pattern in REM sleep, may result from the maturation of the targets of these brainstem systems, the modulation of these generator mechanisms by developing systems, or a relatively subtle maturing of connections within the REM sleep generator systems. This work pushes the probable organization of the REM sleep generator system in rats back to before one week of age, possibly to an in utero stage.

What does all this say about the function of REM sleep? Although we are left with the same initial speculations, the neonatal model provides a different perspective for approaching these functions. It is particularly useful to know that key elements of the REM sleep system are present in neonatal rats, since these animals are ideal subjects for in vitro studies of tissue slices [31,32]. It is not practical to perform in vitro experiments on the adult brainstem. However, there has always been some question as to whether studies of neonatal brainstems would be applicable to the question of adult REM sleep mechanisms. One can now imagine examining the metabolism and membrane characteristics of these critical cell groups as a means of gaining better insight into REM sleep function. However, as Karlsson et al.'s work demonstrates [21], most of the neurons of interest are not homogenously concentrated in any easily targeted region. Identifying the individual neurons of interest in vitro remains a challenge. This challenge will have to be surmounted in order to identify the control mechanism and better understand the function of REM sleep.

Sunday, May 08, 2005

The Tar Heel Tavern - Derby Edition

Tarheel Tavern

Welcome to The Tar Heel Tavern, weekly blog carnival showcasing the best of North Carolina blogging.

This is the weekend of the Kentucky Derby, so, in that vein, let me introduce today's racing contestants.

In starting position #1 is Charlootting, trained by Andy Clarkson of The Charlotte Capitalist stables. In the pre-race interview, Andy said: "Complain all you want about the Charlotte tax increase. But in order to fight taxes, you need to cut spending. I have some ideas on where the priority cuts are. And they are big...". Is he really talking about cutting corners during the race? Sometimes the trainers' lingo is a little obscure....

Maximilian Longley trains Thoroughbreds at Words Fitly Spoken. This year, his Derby hopeful is appropiatelly named Fred Phelps. Max says: "Come on, Fred, make my day!"

Jon Lowder trains his own horses. He is hoping that So Long, Newspapers is the ticket this year.

Chris Weaver is well-known not just for his racehorses, but also for his photographs of them, as he is a TV photojournalist in his spare time. He has been grooming Fear Factor for this race. Apparently, the barn gossip about Hazzardous Materials, a horse withdrawn from the race at the last moment, testing positive on doping control turned out to be a false alarm.

Ron Hudson has two horses in this race: No Verbs Required and PCD Fallen Cake. Ron is hoping PCD does not humiliate him, while No Verbs makes you cry...

Nina keeps her horses at A Sort Of Notebook Farms in Waterfall, in the mountains. Will the years of training in the fresh mountain air help Voice Blogging win this time around? We'll wait and see. The stable-mate Web Blogging still looks stronger to me (and to Nina, or so I heard).

Phin has prepared his horse in secret, thus Scent is a complete mystery to the bookies and the audience alike. A surprise win can get you some nice money! Or does the name implies this horse stinks?

Ogre is trying to fool us into NOT betting on his horse, by naming the colt Lottery Losers. Don't be fooled! I've seen him at his last pre-dawn training and that horse is FAST!

George at Dirty Greek Farm (actually a spotlessly clean farm) is preparing to load Waynesville Cleansing into the starting stalls. What's up with all that cleanliness?

Pam also has two horses in the race. Waynesville Fiasco (half-brother of George's Waynesville Cleansing in the neighboring starting stall) is highly unlikely to be a fiasco by finishing last, while huge and gorgeous chestnut Our Bodies, Ourselves will make some in the audience feel nostalgic for the good old Big Red.

Stewart Pittman of Lenslinger Stables is saddling up Phantom Of The Midway. I heard this horse was stopped by cops for speeding during his morning runs!

Coturnix runs two stables and each has a horse in this race. Equestrian Past is a little winded and long in the pastern and Seasonality has not yet reached his peak this season. Underdogs, for sure, but at least they look pretty.

The above list contains horses signed-up (with enormous entry-fees) by their owners back when these horses were yearlings. However, in this race the Secretary?Handiccapper is allowed to add more horses according to their track-record and the Racing Form. So, here they are, the Secretary's List:

Melinama of Pratie Place brings well-known and expensive Wedding Greed.

AnonyMoses brings Proof. At the end of the race, the proof will be in the pudding (Yorkshire pudding?).

Jean of After Deadline is hoping that Runaway Story runs away with the field.

Arse poetica has a pretty chestnut Dingo in the race. If only looks could kill...

CathColl's entry is a huge black colt Market-Based Coffin.

Chewie is hoping that Trickle Up will trickle up to the finish-line and surprise everyone.

Sally of Green Space is in a good mood, as Good Cheer looks ready to go.

Jude of the Iddybud Racing Stables has high hopes for her Book Table.

Lalitree brought a real beauty: Flickr Reflection.

Littlebear is going to be a Pain In The Ass for all other horses.

Mike of Mungovitz End is a new-comer to this race, with Ugly Kids.

Patrick Eakes owns, trains and rides his own American Hero.

Pirate's Cove is grooming his Weekend Survey.

Walloper is a Pseudonymous UNC Student. Her entry: Virgin Mary .

Robust MacManly Pants is bringing an aptly-named soon-to-be-a-gelding Spokane Mayor.

Silflay Hraka has the only grey in the race: Iraqi Gecko.

Stinging Nettle mounted The Prince.

Satori in Stereo brought Levity.

Southernrants is Sue's Place. Her mount is Time Travel.

This year an underdog won the real Derby, and another two underdogs came in second and third. So, who do you think is going to win here? Who is our Giacomo?

And once the race is over and the dust settles, hang around a bit more. Circadiana may not be Churchill Downs, but there is some good wine and you may find something interesting anyway if you don't fall asleep. And don't forget to come back next week. The racing calendar continues at Pam's House Blend racetrack. See all y'all then and there! And dont' forget to bring your friends along.

Saturday, May 07, 2005


So far, I have directed all my attention to daily - circadian - rhythms, and pretty much ignored other rhythms that correspond to other cycles in nature. Another obvious cycle in nature is the procession of seasons during a year.

Just as an environment during the day is different from the same environment during the night and thus requires different adaptations for survival, so the winter environment and the summer environment present very different problems for an organism's physiology to solve. If one thinks of the circadian clock as a relay timer that orchestrates switching on the "night adapatations" in the evening and "day adaptations" in the morning, then what mechanism plays an analogous role over the course of a year?

There are a number of obvious changes in the environment that occur as a year progresses. It is cold in the winter and hot in the summer. It snows in the winter, and there is a lot of rain during spring and fall. It is easy to find food during the warm season, but very difficult during the winter. It makes sense that organisms would evolve physiological mechanisms that allow them to allocate energy-expensive and risky activities (e.g., reproduction, parenting) to the times of the year when food and cover are abundant, while switching to a more energy-saving mode in the winter.

It also seems wise to be able to predict changes before they happen: not starting a big reproductive effort while the weather is good if it is going to turn cold and nasty just at the time the young are born. Interestingly, it has been found that many mammalian species harbor a subset of individuals that do not respond to seasonal cues - they are quite capable of breeding during the winter. This is an evolutionarily risky strategy, but the pay-off is large whenever the winter is particularly mild. Such non-responsiveness has been studied in a number of species, particularly white-footed mice, and was easily artificially bred in Japanese quail.

One such mechanism for governing biological seasonality is the circannual clock (or "calendar"). In many organisms (even when kept in constant conditions in the laboratory), certain events, e.g., reproductive maturation and behavior, occur with a precise rhythm whose period is close to (usually a little shorter than) 365 days. Not much is known about the physiology of circannual rhythms, though. Deletion of the SCN in rodents does not eliminate circannual rhythms, for instance, suggesting that circannual clock is a separate mechanism from the circadian clock and is also located elsewhere in the brain or body of the animal.

Freerunning circannual rhythms have periods too different from 365 days to be accurate on their own. They have to be entrained to the actual year, in a manner similar to the way circadian rhythms need to be entrained to the day/night schedule. Circadian rhythms can be entrained by a large variety of cues (e.g., temperature cycles, noise, social cues, cycles of magnetic field changes, barometric pressure cycles, etc.), but by far the strongest cue is light. Changes of light intensity over the course of 24 hours are the universally most-utilized entraining agents in nature, because they have the greatest predictive power: no other cue is as reliable. How about circannual rhythms?

Depending on the geographic region, a number of environmental cues serve as dominant triggers for annual physiological changes. Rain (e.g., monsoons), temperature and social cues can trigger reproductive maturation and behavior, entry into hibernation, or start of annual migration. These cues are sometimes called "proximal cues" as they more or less directly affect the onset of annual biological events. However, the proximal cues can only work if the organism is already 'prepared' for them.

In very unpredictable environments, e.g., in deserts in which it may not rain for years, the organisms are at a constant readiness - always receptive to proximate cues. A well known example is a finch living in deserts of Australia. When it rains, it is ready to mate and lay eggs within a day or two.

In almost constant environments, e.g., at the poles and at the equator, the plants and animals may follow freerunning circannual rhythms. For instance, elephant seals have a breeding season every ten months, thus falling in a different month every year.

In most areas of the planet, however, there are sharp and predictable changes between the seasons. The "ultimate cue" that prepares the body for the emergence of proximal cues is the gradual change in daylength - photoperiod. Unlike fluctuations in temperature, humidity, or even light-intensity, photoperiod is a reliable cue. On March 21st of EVERY year, photoperiod is LD 12:12. At any latitude, the photoperiod is always exactly the same on the same date of the year. No other cue can come close to matching such precision. Thus, it is not surprising that almost all organisms, even those living on the equator and the poles, are capable of responding to changes in daylength, at least in the laboratory. Seasonal Affective Disorder (SAD) - or "Winter Blues" - in humans is thought to be a response to changes in photoperiod. It is not cold weather that makes you depressed in winter, it is the short days and long nights.

In many organisms circannual rhythms are too weak, or even undetectable, to be able to drive a seasonal rhythm of responsiveness to the environment, let alone a rhythm of actual behavior. Still, no matter if the circannual rhythm is robust, weak, or undetectable, changes in photoperiod are capable of entraining (robust) or directly driving (weak) circannual rhythms.

Next couple of posts will focus on the phenomenon of photoperiodism and what we have learned about the mechanisms organisms use to translate changes in daylength into seasonal biological events. You should not be surprised that evolution used an existing timer - the circadian clock - to measure the length of the day. More on that tomorrow...

Category: Clock Tutorials

ClockQuotes: Golda Meir

I must govern the clock, not be governed by it.
- Golda Meir

Thursday, May 05, 2005

ClockQuotes: Dave Allen

We spend our lives on the run: we get up by the clock, eat and sleep by the clock, get up again, go to work - and then we retire. And what do they give us? A bloody clock.
- Dave Allen <

Can You Help?

OK, here's the deal. Both of my cars just had major repairs. That ate into our little savings nest egg - about two months worth of rent. We will pay next months rent, but that leaves almost nothing for other bills or food. We should be able to recover by next month or two. Mrs.Coturnix who is a night-shift ICU nurse is going to do some overtime. I teach adults at a community college and my paychecks are small and far apart, but one is coming in two weeks, and the next class also starts in two weeks. I am considering taking another job, but that will, even more, slow down my dissertation writing. Two cars are essential, given the strange work schedules and having to take Coturnix Jr. and Coturnietta to two different schools every morning. Hope for a newer better computer are now gone. That is why I have just installed a PayPal button on the sidebar. A hundred regular readers with one-time donation of $10 would pay for rent for the next month and get us back into solvency. I hate asking for help, but today, I just have to. Thanks!

Heinrich on Johnson: Adaptive Function of Circadian Clocks

Heinrich (of She Flies With Her Own Wings blog) wrote a very thoughtful post about the adaptive value of circadian clocks, inspired by a recent review by Carl Johnson (which I will link to and comment on soon). This post is also a part of the most recent edition of The Tangled Bank , the blog carnival of science, nature, medicine and environment, posted on Buridan's Ass . I warmly recommend you go and check it out.


Tuesday, May 03, 2005

Sleepdoctor On Narcolepsy

The newest addition to the sidebar, Sleepdoctor, is a psychiatrist and a sleep specialist. He has just finished a series of posts about narcolepsy. Here are parts One, Two and Three.

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