Capstone Presentation for BI412: Neuroscience. Provides a basic introduction to sleep before exploring the underlying mechanisms and consequences of sleep deprivation.
When I was trying to pick my capstone project I was torn between further exploring my summer research and doing something completely different. Obviously, I made the former choice.
I made the decision to research sleep because it is one of the few topics in science that affects everyone and for the most part does so without preference. Obviously there are risk factors for certain sleeping disorders, but at the end of the day, sleep is something which benefits everyone in a similar, if not completely understood manner. Furthermore, we all need sleep for proper functioning, even those of us who claim that we don’t, and we all know how awful we feel when we don’t sleep. There are these immediate effects of sleep restriction that you don’t often get in many other negative health behaviors. And most importantly…who doesn’t love to sleep?
This is the rundown of today’s presentation. The first half will focus on normal sleep patterns while the second examines sleep restriction, with a focus on CSR which I’ll talk more about when we get there. Much of the background I provide is directly related to my summer project. For example, when talking about the stages of sleep I focus mostly on the EEG outputs for them and this is so I can introduce the terminology necessary for my discussing CSR.
When talking about sleep, the circadian rhythm or circadian clock is essentially an internal pacemaker that uses the light/dark cycle to cue the body about sleep and wakefulness. There are other circadian rhythms in the body (e.g. eating). The suprachiasmatic nucleus, or SCN, is known as the master circadian clock because it regulates all circadian rhythms in the body. It is located deep in the hypothalamus and contains 2 subnuclei, the core and the shell, which are collect inputs and generate circadian timing signals, respectively. Info is brought here from the retinohypothalamic tract which is responsible for synchronizing the 24-hour circadian clock with the light-dark cycle. In the SCN, the RHT releases glutamate which acts at both NMDA and non-NMDA receptors, as well as through numerous intracellular signaling molecules and immediate-early response genes (e.g. c-Fos). The circadian rhythm itself is generated through a feedback loop which involves 9 genes. The autoregulatory loop causes rhythmic transcription and expression of various so-called “clock” genes which coordinate circadian rhythms in metabolism, electrical activity, and the release of NTs of SCN neurons. These processes, in turn, transmit circadian timing signals throughout the body.
Working at the same time as the circadian rhythm, and almost in opposition to it, is adenosine, which is responsible for the homeostatic sleep drive. This drive determines your level of sleepiness based on your amount of prior wakefulness. The longer one is awake, the higher his or her extracellular adenosine levels. Adenosine, therefore, is considered a sedative because high amounts of it result in high levels of sleepiness. Caffeine is one of the antagonists that can be used to counteract sleepiness, as I’m sure we all know very well! Adenosine is believed to work in an inhibitory fashion, specifically by inhibiting wakefulness-promoting neurons in the basal forebrain and cortex via hyperpolarization through the A1 receptor. Adenosine may also cause its sedative effects through prostaglandin D2 which is produced largely by mast cells. Though the precise mechanism for this was not discussed in the article, it is known than an increase in D2 levels in the subarachnoid space is accompanied by an increase in adenosine levels.
There are six stages in the sleep-wake cycle. These fall into one of three categories: wakefulness, NREM, and REM sleep. NREM can be further divided into 4 stage, aptly named stages 1-4, with 1 being the lightest and 4 being the heaviest. You can see the physiological differences in the image on the right. The image on the left shows the EEG outputs for the different stages of sleep and this is how we learn a lot about sleep and what effects different drugs or measures, such as sleep restriction, have on sleep, both in general and for specific stages. Just to do a brief overview, wakefulness is marked by very high frequency, low amplitude waves. Stages 1 and 2 are known as light sleep and Stages 3 and 4 are known as Slow Wave Sleep (SWS). Stage 3 is characterized by sleep spindles (short burst of activity) and Stage 4 by delta waves (0.3 to 3.0 Hz)
Sleep’s homeostatic regulation tells us that the intensity of sleep increases in proportion to the duration of prior wakefulness. Sleep intensity is reflected, in mammals, by NREM Slow Wave Activity (SWA) which occurs during SWS and “increases exponentially as a function of previous waking, peaks at the beginning of sleep, and declines exponentially with the progression of sleep.” It has been found that LTP, which is associated with an increased synaptic load, leads to enhanced amplitude when occurring in the presence of NA. Cirelli, et al. ’s 2005 study showed that the depletion of NA led to a blunted SWA response, likely because of a reduction in LTP during wakefulness. It is important to note that this was the only effect the depletion had on the EEG spectrum. Cirelli, et al. proposed that NA may work through beta-adrenergic receptors to mediate sleep intensity.
So what exactly is sleep restriction? Well sleep restriction is divided into two types, acute and chronic. Acute sleep restriction lasts for 6 to 24 hours while chronic lasts for more than 24. The human analog would be an all nighter versus just not getting enough sleep over and over again, as many of you just showed you do. My focus is on CSR since much is already known about ASR AND because recent studies have found that the response to CSR is vastly different than to acute. It essentially boils down to the idea of CSR being mediated by an allostatic load rather than a homeostatic one. With ASR you pull an all nighter and the next night, you crash. You sleep longer and deeper, and EEG output would show a huge increase in NREM delta power. With CSR, on the other hand, it was discovered that you only get these homeostatic responses during the first sleep opportunity after the restriction. (Talk about graphs). From SD day 2 on, your levels of NREM sleep and the total time you spend sleeping reverts back to baseline levels. During recovery sleep, the levels remain the same as well. Therefore, the lost sleep is never made up (no not even through naps and sleeping in on the weekends). It is believed that the stress response, often seen as a confound in sleep studies, is extremely important in CSR. It is believed that physiological stress caused by CSR adds to the allostatic load which, in turn, feeds into the sleep-wake cycle and causes the adaptive effects seen. Finally, it is important to note that only sleep intensity is affected by this and not sleep latency which leads us to believe that there are two separate regulatory systems.
Current research is looking at NA and the β-AR in an attempt to elucidate the neuronal mechanism responsible for the adaptive responses of sleep time and intensity seen during CSR. It has been found that -AR mRNA receptor levels exhibit an inverse pattern during CSR, decreasing significantly during the first sleep opportunity and returning to baseline levels thereafter. It has also been shown that -AR is activated during sleep, as seen in the double labeling of the receptor and c-Fos. Combined, these results suggest that -AR and NA may play a role in modulating sleep intensity, although much research still needs to be done.
Before discussing the effects of CSR on specific populations, its important to understand its effects in general. This study compared waking neurobehavioral and sleep physiological functions of individuals undergoing CSR to those undergoing TSD. There were 3 CSR groups (4, 6, and 8 hours of sleep) and one TSD group (3 days without sleep). Neurobehavioral performance measures were taken every 2 hours while awake. The results showed a dose-response relationship between the amount of CSR and performance on the performance measures. Furthermore, the performance continued to erode as the total sleep debt accumulated over the course of the 14 day study. Such results were also seen for the TSD group, leading them to conclude that even moderate chronic sleep restriction can have a sizeable impact on cognitive importance.
The results from the Van Dongen, et al. obviously are very worrisome for college students who find themselves practicing both TSD and CSR. When you combine them with the results from Kim, et al. , specifically that sleep debt continues to accumulate rather than be made up past the first sleep opportunity, the news becomes even gloomier. Traditional methods of “making up” sleep, such as napping and sleeping in on the weekends, are not effective but rather are “band-aids” for the larger problem. The issue of CSR and college students was taken up in an article for St. Joseph’s University. Perhaps the most interesting part was that students seemed aware of the detrimental effects of CSR but felt it was, as one girl quoted, “a winless battle.”
College students are not the only ones suffering the ill effects of CSR. Business executives and managers, lawyers, and doctors all feel the pressure to sleep less and do more. I feel these two quotes sum everything up. *READ* The lifestyle of business executives challenges their abilities to function well based on four major sleep-related factors: the homeostatic drive for sleep, the total amount of sleep gotten over the course of several days, the circadian phase, and sleep inertia, or the grogginess felt upon waking. Czeisler also points out that sleep restriction is not just a personal health and mental concern, but also a public one. When individuals deprive themselves of sleep, they put others at risk by doing things such as driving impaired, inadequately performing regular tasks at the daily job, and taking on challenges, such as operating machinery and guarding secure sites, that they are not mentally prepared to do. He believes it is a big enough problem that, similar to workplace policies against drinking, drugs, and sexual harassment, corporate sleep policies should be implemented.
Little research has been done on sleep architecture and lactating mothers. Adequate sleep has been shown to play a role in preventing post-partum depression but little is known about the mechanism. Blyton, Sullivan, and Edwards conducted a study in which they examined the sleep architecture of lactating mothers, bottle-feeding mothers, and controls with the hope of quantifying the sleep of fully lactating women and investigate whether lactation alters sleep quality and duration. Their results showed that lactating mothers spend more time in SWS and less time in light NREM (stages 1 and 2) as compared to the other two groups. (Graphs) Because the results diverge from previous research discussed here, and because some research has already been done on the role of prolactin and sleep, they concluded that it is lactation and the associated complex interaction of the neuroendocrine system which causes this change in sleep architecture. Again, the mechanism is still unknown.
Like any good scientific enigma, the more that is discovered about sleep, the more questions that arise. Unlike many scientific topics, however, the answers to these questions can affect all areas of an individual’s life, including health, mood, interactions with others, personal and public safety, and more. And though it is often said that you can sleep when you are dead, waiting until then to do so may be the very thing which gets you there.
![Why Sleep? ,[object Object],[object Object],[object Object],[object Object]](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)