Sleep-Wake Homeostasis: How Our Internal Body Clock Regulates Our Sleep

Sleep is vital to our good health and well-being. Quality sleep is rejuvenating and restorative. It promotes muscle growth and repair, and removes waste from the brain. It strengthens memory and helps us solve problems and learn. 

When we have difficulty falling asleep, or our sleep is disrupted, it can result in physical and emotional problems. Long-term sleep deprivation can lead to even more serious and chronic conditions including cardiovascular disease, cognitive diseases, metabolic disorders, and obesity. 

Under normal circumstances, two systems in our bodies interact to influence our sleep as well as our wakefulness — sleep-wake homeostasis and circadian rhythm. When these two systems fall out of sync (sleep restrictions can happen for a variety of reasons) our sleep quality suffers. Understanding these two systems and how they work together can help you regain your good night’s sleep.

What is Sleep-Wake Homeostasis? 

Homeostasis is any internal biochemical system that regulates the body’s internal environment with the goal of maintaining properties such as body temperature and blood sugar, in a stable and relatively constant condition.

It is quite intuitive in its operation: the longer we have been awake, the stronger the desire and need to sleep becomes, and the greater the likelihood of falling asleep; the longer we have been asleep, the more pressure (or, sleep pressure) to sleep dissipates, and the greater the likelihood of awakening. 

How Does Sleep-Wake Homeostasis Work?

The actual mechanism of sleep-wake is relatively poorly understood, despite years of research. 

But what we do know is that an endogenous (i.e. naturally produced by the body itself) sleep-regulating substance, or substances, builds up in the body’s cerebrospinal fluid during our waking hours, which has the effect of increasing the pressure to sleep the more it accumulates. This pressure is only released by the act of sleeping itself, during which the levels of the sleep-regulating substance in the body rapidly declines.

The best known of these sleep-regulating substances (although probably not the only one) is adenosine. Adenosine operates as a neuromodulator in the brain, and has the effect of inhibiting many of the bodily processes associated with wakefulness, particularly those involving the neurotransmitters norepinephrine, acetylcholine and serotonin.

This supports the theory that the body’s regular desire for sleep stems, at least in part, from the brain’s periodic need to replenish low stores of energy: in 1995, Craig Heller and Joel Benington proposed this theory, based on the observation that, as the brain’s glycogen energy stores are depleted throughout the day, extracellular adenosine builds up, and then, during sleep, the adenosine is removed and replaced by new glycogen.

Experiments have definitively shown that high levels of adenosine lead to sleepiness. Studies in animals have shown that blocking adenosine‘s actions in the brain increases alertness, while injections of adenosine or similar compounds induce apparently normal sleep. 

Also, adenosine concentrations in the brain shoot up dramatically in animals forced to stay awake. Commonly used stimulants, like the caffeine in coffee, tea, cola and energy drinks (as well as the theophylline in tea and chocolate), work as adenosine antagonists or receptor blockers, inhibiting or dampening its sleepiness effect, and thereby maintaining alertness.

The main sleep-wake homeostatic mechanism appears to refer specifically to non-REM (rapid eye movement) sleep, and particularly deeper slow-wave sleep. Thus, in general, the pressure to sleep is a pressure to enter into deep non-REM (nREM) sleep, a pressure that is only relieved by a period of actual deep nREM sleep. It is still not entirely clear whether there is a similar mechanism for REM sleep, although the indications are that there may well be.

So, the loss of REM sleep also leads to an increase in the tendency to enter REM sleep (also known as rebound sleep), but, unlike the case with slow-wave sleep, this loss appears to be compensated up to a certain extent only, and with certain differences between different animals. Also, two or three nights of recovery sleep can usually remedy situations of total sleep deprivation and return individuals to a natural sleep pattern. 

Sleep-Wake Homeostasis and Sleep Inertia

On awakening in the morning, a phenomenon known as sleep inertia sometimes takes hold, which manifests itself as a general feeling of grogginess and impaired motor activity which may last for up to half-an-hour after waking. Sleep inertia may be accompanied by a distinct feeling of wanting to return to sleep, even at times appropriate for normal waking.

This is most likely to occur when waking from deep slow-wave sleep rather than from light sleep or REM sleep, and may be more severe (and last longer) after waking from a sleep period or nap following a prolonged period of wakefulness or accumulated sleep debt or sleep deprivation. It may be caused by an excessive build-up of adenosine (through the normal sleep-wake homeostasis process) that has not fully dissipated by the time of awakening.

Interestingly, to some extent, light exposure seems to directly affect alertness, performance and mood through the sleep-wake homeostatic process, in addition to its essential part in regulating the circadian clock.

How Does Our Circadian Clock Regulate Sleep?

When we hear about the sleep-wake process, we often think of the circadian clock, the internal 24-hour clock in our bodies that cycles around in predictable patterns every day telling us when to sleep, when to wake up, when to eat, and so on. This master clock is operated by a group of neurons in the brain called the suprachiasmatic nucleus which takes cues our body sends when it senses changes in the environment.

For example, when we see the sun setting in the sky and the darkening of night fall, sensors in our eyes send a message to the suprachiasmatic nucleus which triggers the production of melatonin, the hormone that makes us sleepy.

Like sleep-wake homeostasis, circadian rhythm plays a role in our sleep by determining our sleep patterns. Both the circadian pacemaker and sleep homeostat work independently but together, play a role in regulating sleep. What is not known is whether the two processes are directly influencing each other.

Sleep Processes: The Regulation of Sleep

The two-process model of human sleep consists of the sleep-wake homeostasis and the circadian rhythm. In summary, sleep-wake homeostasis creates a drive to balance sleep and wakefulness whereas the circadian phase, governed by the internal biological clock, regulates timing of when you sleep and when you are awake.

The idea of circadian regulation and sleep homeostasis working together to influence sleep propensity was first proposed in the early 1980s by Swiss sleep researcher Alexander Borbély along with Serge Daan and Domien Beersma. 

Their sleep research was based on quantifying sleep intensity through EEG (electroencephalographic) recordings, and has been widely influential and strongly influenced for decades in the field of circadian neurobiology. About a decade later, sleep researchers Derk-Jan Dijk and Charles A. Czeisler further expounded on this theory. 

In an analysis published in the journal Neuroscience Letters Dijk and Czeisler, wrote “the circadian pacemaker and the sleep homeostasis contribute about equally to sleep consolidation.” Together, these two oscillatory processes during a 24-hour period are uniquely timed to facilitate the ability to maintain a consolidated amount of sleep at night as well as a consolidated bout of wakefulness throughout the day, they wrote.

Each of these processes are influenced by our genes. But they are also influenced, either directly or indirectly, by various external factors such as food, drugs, ambient temperature, meal times, stress, exercise, alarm clocks, and so on. This can greatly affect the quality and quantity of our sleep. In general, these factors can increase awakenings and interfere with deep sleep. 

How the Two-Process Model Works

During the day, homeostatic sleep drive typically increases, making you sleepier and sleepier as the day goes on. Meanwhile, the circadian drive begins to wind down from the arousal phase and begins the release of sleep-inducing melatonin as evening falls. This causes the opening of the so-called sleep gate, the point where homeostatic sleep drive is at its farthest distance from circadian drive for arousal. 

At this point, it is believed that neurons in the brain settle into sleep and, once enough of them are at rest, your body follows suit. During the night as you sleep, sleep homeostasis quickly dissipates as circadian-regulated melatonin production continues. 

By morning, the circadian clock shuts down production of melatonin and the circadian alert system cranks up activity again. This is when the circadian drive for arousal overcomes the homeostatic sleep drive, triggering wakefulness. 

Stages of Sleep

Sleep is typically divided into REM and non-REM sleep. Together, they makeup a single sleep cycle. During a typical 7-9-hour night’s sleep, you can expect to cycle through four or five sleep cycles. To better understand how sleep-wake homeostasis and circadian rhythmicity impact sleep, let’s take a closer look at the stages of sleep:

• Stage 1 & 2: Light sleep: When you first lie down to sleep, your body begins to transition to deeper sleep by relaxing your muscles, your body temperature drops, and slowing your heart rate and breathing. During Stage 2, sleep spindles may occur in response to environmental stimuli, such as noises in the bedroom. These bursts of coherent brain activity are visible on a sleep EEG. It is easier to be awakened during light sleep.
• Stage 3 & 4: Deep Sleep: As you fall into a deeper sleep and your body moves into a rejuvenating and restorative phase. During this time your brain develops slow wave activity, blood pressure drops, blood flow increases to your muscles, tissue growth occurs, and cells begin to repair themselves. It is more difficult to wake someone from deep sleep and when they do awaken, they are disoriented or groggy.
• REM Sleep: Rapid eye movement, or REM, sleep is vital to your sleep process and helps with memory, learning, and problem solving. This is when you dream. During this stage of sleep breathing and heart rate increase, brain activity is high, sleep paralysis kicks in to stop you from acting out your dreams. Your first REM stage begins within about 90 minutes sleep onset and your first dream sequence will last only about 10 minutes. Afterwards, you return to light sleep and the process begins again. Through each stage, REM will last longer — up to an hour during your last cycle.

When Sleep Processes are Disrupted

Biological circadian system and sleep-wake regulation can be disrupted in a variety of factors:

• Light: Light can not only interfere with sleep directly, making it difficult for us to fall asleep, it can also indirectly influence the timing of our internal clock by interfering with the natural release of melatonin, which helps us fall asleep at night. 
• Jet lag and shift work: Irregular work schedules and travel across time zones can influence our ability to sleep at appropriate times during a 24-hour period. It can also interfere with sleep stages and cause problems like insomnia and excessive daytime sleepiness. 
• Pain, anxiety, depression: Psychological conditions can disturb sleep struction and sleep duration. 
• Medical conditions: Medical conditions that cause chronic pain or general discomfort can interfere with sleep. 
• Changes the the timing of sleep: This includes staying up later than usual or waking earlier than usual
• Cognitive problems: such as Alzheimer’s disease or Parkinson’s disease can cause circadian rhythm disturbances. 
• Medications: Commonly prescribed drugs that interfere with sleep include antihistamines, beta blockers, alpha blockers, antidepressants, and sleep medicine.
• Other substances: Coffee, alcohol and nicotine can adversely affect sleep. 
• Genetic mutations: It has been demonstrated in sleep deprivation studies that mutations in so-called clock genes can interfere with sleep homeostasis. 

When the biological circadian system and sleep-wake cycle are disrupted, it can cause sleep loss and result in sleep disorders such as insomnia, circadian rhythm disorders or idiopathic hypersomnia (also called sleep-wake syndrome).

A study published in the journal International Review of Psychiatry suggests that sleep-wake misalignment can cause cause unscheduled secretions of insulin (regulates blood sugar levels), leptin (regulates hunger), and norepinephrine (increases stress), and increase the risk of heart disease, diabetes, obesity, and psychiatric conditions. 

Summary

The human body is a miraculous machine. Sleep is its way of restoring and rejuvenating itself using the two-process model which relies on the interaction of sleep-wake homeostasis and circadian rhythm. But when these processes fall out of balance, it can result in a sleep deficit. Understanding them can restore quality sleep and improve overall well-being.