Video: Sleep and wakefulness

There’s nothing that compares to a good night’s sleep. That feeling of waking up, feeling refreshed, and ready to take on the day. On the other hand, waking up from a night of vivid nightmares is not a very pleasant experience. What exactly happens when we sleep?

In this tutorial, we’re going to have to stay alert as we learn about the physiology of sleep and wakefulness.

Sleep is a state of unconsciousness. But so is a coma. So, what then is the difference between the two? Sleep is a temporary state of unconsciousness from which one can be awakened or aroused by external or internal stimuli. We know that we need to sleep and everyone experiences the effects of not having slept well enough from time to time, perhaps after a long night of studying before an exam. Our concentration suffers, productivity declines, and at some point our bodies need to catch up on that lost sleep.

So why do we sleep?

For something that we spend nearly a third of our lives doing, we know shockingly little about the need for it. Some theories are that we need to sleep for memory consolidation, for immune competence, or even for metabolic recovery of the brain. The reason is unclear, but one thing is for certain. We need to sleep.

Sleep happens in stages, categorized into rapid eye movement sleep and nonrapid eye movement sleep. Rapid eye movement sleep, also known as REM sleep, involves rapid movements of the eyes -- yes, while we’re asleep. Nonrapid eye movement sleep, also known as non-REM or NREM sleep, obviously does not have these rapid eye movements.

Our eyes thus move during some stages of sleep, but what about the activity in our brains? Contrary to what one might think, our brains are not inactive at night. The activity can be seen on an electroencephalogram or an EEG. This EEG is a recording of electrical activity in the brain. These brain waves are thought to represent communication between regions of the cortex and deeper brain structures like the thalamus. The activity is picked up by electrodes placed on the surface of the scalp.

The pattern of waves seen in the EEG depends on the level of consciousness. When our eyes are open, we experience a lot of sensory stimulation. The EEG records low voltage and high frequency waves, known as beta waves. These waves have a frequency of 13 to 30 Hertz, meaning that the electrical signal oscillates 13 to 30 times per second.

When we close our eyes, sensory stimulation reduces. In this relaxed, yet awake state, the waves lower in frequency and increase in amplitude. These are alpha waves, with a frequency of 8 to 13 Hertz. In the right environment with eyes closed, drowsiness ensues and we fall asleep.

Thus begins the first stage of sleep -- nonrapid eye movement sleep or non-REM. Non-REM sleep has four stages -- Stage I, II, III, and IV. They can also be classified into N1, N2, and N3 sleep, where stages III and IV are combined into the N3 category.

N1 is the initial stage of drowsiness and light sleep, where the EEG waves start to slow down. Thus, the frequency reduces while the amplitude increases. These are theta waves with a frequency of usually 4 to 8 Hertz. It’s easy to be awakened from this stage since it’s the lighter stage of sleep. As the night progresses, sleep deepens.

From N1, we enter N2 where the waves get slower. During the N2 stage, these low-frequency waves can be interrupted by sleep spindles, which are clusters of spindle-shaped waves at frequencies of 12 to 14 Hertz. There can also be K-complexes, which are large biphasic waves.

Some people grind their teeth at night, a condition known as bruxism. They usually experience such episodes during this N2 stage of sleep. The EEG waves during this stage are of a lower frequency than the theta waves of N1, but not as low as the large delta waves seen in N3.

These delta waves are also known as slow waves. They have a large amplitude and the lowest frequency, less than 4 Hertz. Hence this stage of sleep is also known as slow-wave sleep. While in this state of deep sleep, it’s quite difficult to be awakened since our ability to perceive stimuli from the external environment is reduced. This is because of a decrease in communication between the thalamus, our sensory relay station, and the cortex.

An individual suffering from sleepwalking, a condition known as somnambulism, can have episodes during this N3 stage of sleep.

During non-REM sleep, muscle tone reduces, but is not lost. We can toss, turn, and adjust our posture during the early stages. Body temperature falls, metabolic rate reduces, the heart rate and blood pressure slow down.

You’d think after N3, we’d enter REM sleep. But sleep actually lightens first from N3 to N2 and then we enter REM sleep.

REM sleep, also known as the R stage of sleep, is very interesting. Instead of the waves slowing down further, they look similar to the beta waves we see when one is awake and alert. However, we’re asleep! That’s the paradox, and thus REM sleep is also known as paradoxical sleep.

During REM sleep, the brain is very active and the eyes have rapid to and fro movements. However, muscle tone is lost during this stage. Why is that important? It’s during REM sleep that we have the most vivid dreams, even nightmares. If muscle tone was intact, our bodies might enact those dreams and nightmares! However, some muscles retain their tone, such as the extraocular muscles and the respiratory muscles.

The threshold for arousal is highest during this stage, making it much harder to be awakened.

During REM sleep, there are other physiological changes as well. The body temperature continues to fall, heart rate and blood pressure can be variable, and penile tumescence can occur.

With that, we come to the end of one sleep cycle. Non-REM and REM stages alternate with each other through the night forming this cycle, with each cycle taking around 90 to 120 minutes. As the night progresses, the duration spent in REM and N2 sleep progressively increases, while N3 reduces. Spontaneous awakening typically happens from REM sleep.

The duration of the stages of sleep varies with age. In infants, the duration of REM sleep is much longer than in young adults. In the elderly, it’s much shorter. In young adults, 25 percent of sleep is spent in the REM stage, with around 4 to 6 REM cycles every night. In a 7- to 8-hour sleep period, that’s nearly 1-1/2 to 2 hours. In infants, nearly 8 hours is spent in REM sleep, while in a 70-year-old, that duration reduces to around 45 minutes.

Every 24 hours, we go through a sleep-wake cycle. But how does our body know when to sleep and when to wake up?

From the time we wake up, over the course of the day, our bodies experience a steadily growing pressure to sleep. This homeostatic sleep drive peaks just before our usual bedtime. One theory for why this happens is that there’s an accumulation of sleep-promoting substances during the waking hours. For example, adenosine.

As the day goes on, the brain metabolizes adenosine triphosphate, or ATP, and generates adenosine. The accumulated extracellular adenosine has receptors in various areas of the brain, inhibiting wakefulness and promoting sleep. Caffeine, in our morning cup of coffee, acts as an adenosine receptor antagonist, which fights this sleep drive.

The homeostatic sleep drive is countered by our inbuilt biological clock, the circadian wake drive. These wake-promoting signals peak midday and start to dip in the afternoon, which is usually when we feel like taking a quick nap. They reach their lowest before bedtime, when they get outmatched by the homeostatic pressure for sleep. Therefore, we fall asleep.

The circadian rhythm is a 24-hour clock governed by the suprachiasmatic nucleus in the hypothalamus, which sets the rhythm for a lot of physiological functions, including body temperature, secretion of hormones such as cortisol and growth hormone, and sleep. This clock works on a 24-hour rhythm based on the light in the external environment, creating a cycle of internal functions that are synchronized to the light/dark cycle of the environment. This is known as photoentrainment.

Light is absorbed by a special type of cell in the retina, known as the photosensitive retinal ganglion cells. Unlike rod and cone cells, which are photoreceptor cells required for image formation, these cells have a special photopigment known as melanopsin.

Light absorbed by these cells results in depolarization. The action potentials are conducted along the retinohypothalamic tract to the suprachiasmatic nucleus located in the hypothalamus. This suprachiasmatic nucleus is the center of circadian control, and it regulates the secretion of a sleep-promoting hormone, melatonin. Let’s see how that happens.

The suprachiasmatic nucleus communicates with the paraventricular nucleus of the hypothalamus. From here, axons travel down the spinal cord to reach the intermediolateral nucleus in the lateral horn of the thoracic spinal cord to be able to stimulate the sympathetic nervous system.

The preganglionic sympathetic axons reach the superior cervical ganglion, from where the postganglionic sympathetic axons carry impulses to the pineal gland, a small endocrine gland that synthesizes melatonin. Using this pathway, the suprachiasmatic nucleus can regulate melatonin secretion, decreasing it during the day and increasing it at night, such that the peak melatonin secretion usually happens between 2 and 4 a.m. in the morning. This is perfectly tailored to its function, which is sleep promotion.

If you’ve traveled across three or more time zones, you’ve probably experienced jet lag. That’s because it takes the suprachiasmatic nucleus time to adjust to the changes in light exposure times and reset our day-night cycle.

Another hormone that follows this circadian rhythm is cortisol. Cortisol is produced by the suprarenal gland and its synthesis and release is regulated by the hypothalamic-pituitary-adrenal axis. Its patterns of release is opposite to that of melatonin.

Our cortisol levels rise towards the morning, peaking minutes before we wake up, and steadily reduce as the day goes on, dropping to their lowest level in the middle of the night. This pattern follows the circadian wake-promoting signals we saw earlier, and plays a role in initiating wakefulness.

Thus the circadian rhythm helps us to know when to wake up and when to go to sleep. But how does our brain actually wake us up and put us to sleep?

Research suggests that we have wake-promoting neurons in the lateral hypothalamic area and sleep-promoting neurons in the ventrolateral preoptic nucleus, a small nucleus in the preoptic area of the hypothalamus. When the suprachiasmatic nucleus senses light during the day, it stimulates the wake-promoting neurons and inhibits the sleep-promoting ones via the dorsomedial nucleus of the hypothalamus. This keeps us awake during the day. When the light dims, the reverse happens and we fall asleep.

Details of how this happens are not completely understood. Like we saw earlier, there are theories that suggest we have regions in the brain that serve as the ascending arousal system and other areas that function as the sleep-promoting system.

The ascending arousal system involves nuclei in the reticular formation of the brainstem, the hypothalamus, and the basal forebrain that project diffusely to the cerebral cortex to keep us awake. These structures use neurotransmitters such as glutamate, acetylcholine, serotonin, norepinephrine, histamine, and orexins to promote wakefulness.

The sleep-promoting system primarily includes small nuclei in the preoptic area of the hypothalamus, such as the ventrolateral preoptic nucleus and the median preoptic nucleus, which use neurotransmitters such as gamma-aminobutyric acid or GABA and galanin to promote sleep.

These two systems work by mutual inhibition. The sleep-promoting system can inhibit the ascending arousal system to promote sleep and vice versa to promote wakefulness. Thus they help us cycle between being awake and asleep, spending very little time in the transition stage.

This is just brushing the surface of the complexity of sleep. Don’t let neurophysiology keep you up at night. Our study units and quizzes at Kenhub are here to help.