Stages of sleep

Stage N1

It is a transitional phase between wakefulness and sleep during which the body “slows down”. It normally has a duration of one to five minutes comprising 5% of total sleep time. It is a phase of light sleep making it easy to wake up during this time. Although the body has not completely relaxed yet there is a decrease in heart rate, muscle tension and body temperature. It is the time in which hypnic jerks (abrupt muscle spasms) as well as a feeling of drifting or falling can occur.

Stage N2

This is the second stage and it represents deeper sleep. It has a duration of approximately twenty-five minutes in the first cycle and lengthens with each successive cycle, taking up in total 45% of a night’s sleep. During N2 the heart rate and body temperature drop as the body enters a more relaxed state. It is also the stage in which bruxism (teeth grinding) takes place in pathological situations.

Stage N3

It is the deepest stage of NREM sleep and is hard to wake from, because communication between the thalamus and the cortex falls and the ability to perceive external stimuli drops. For some individuals, even loud noises higher than 100 decibels during N3 will not lead to an awake state. If someone is awoken during this stage, they will have a temporary time of mental fogginess, also characterized as sleep inertia. In this stage the human body repairs and regrows tissues, promotes bone and muscle growth and enhances the immune system. Even though NREM is often considered as a “dreamless” sleep, dreams and even nightmares can actually occur in this stage of slow-wave sleep. Dreams in this stage are more like an extension of thoughts from everyday events during wakefulness. Unlike nightmares, they tend to be more conceptual and logical and are typically not recalled. N3 is also the stage in which bedwetting and sleepwalking can occur. As people age, they spend less time in this stage and more in N2.

Brain waves in awake state

As already mentioned, wakefulness can be subdivided into an alert and a tired state. During the alert state, beta and gamma waves are the predominant wave pattern whereas in the tired state, alpha waves are recorded. Among the four classic brain waves, beta waves have the highest frequency and the lowest amplitude. Gamma waves, recorded in the most active states, have an even higher frequency. They appear in engaging activities such as problem solving. On the other hand, alpha waves are slower waves characterized by lower frequency and are more dominant as we start to become drowsy.

Brain waves in N1

In stage N1 theta waves are mainly recorded which are characterized by low frequency and low voltage. Initially, alpha waves from the awake state dominate but as the brain transitions to the N1 stage theta waves begin to replace them.

Brain waves in N2

During stage N2, theta waves are periodically interrupted by sleep spindles and K complexes. Sleep spindles are brief, powerful bursts of neuronal activation, which take place in the superior temporal gyri, anterior cingulate, insular cortices and thalamus, facilitating the calcium entry into cortical pyramidal neurons. K complexes, by contrast, are high-amplitude biphasic waveforms generated in the cortex, each lasting around one second. They fall within the delta frequency range but appear as single transient events rather than continuous delta activity. Both sleep spindles and K complexes are thought to protect the brain from waking up, as well as play an important role in synaptic plasticity processes, long term memory formation, sleep integrity and sensory processing.

Brain waves in N3

In N3 the recorded brain patterns are delta waves which have the lowest frequency and the highest amplitude.

Brain waves in REM

During REM sleep beta waves are mainly recorded and occasionally gamma waves, similar to an awake individual during cognitive activity. This finding confirms the highly active state of the brain in REM. Due to this intense brain activity opposed to the paralysis of the skeletal muscles, REM sleep is often characterized as paradoxical sleep.

Hypothalamus

Sleep is controlled by several interconnected regions of the brain, with the hypothalamus serving as the primary control center for sleep and arousal. Within the hypothalamus, the suprachiasmatic nucleus (SCN) regulates our circadian rhythms by responding to light exposure, aligning the sleep-wake cycle with the external day-night pattern.

Brainstem

The brainstem, which includes the pons, medulla oblongata, and midbrain, facilitates transitions between wakefulness and sleep. The raphe nuclei in the lower pons and medulla contain serotonergic neurons that modulate the sleep-wake cycle. These neurons fire fastest during wakefulness, slow during NREM sleep, and fall silent during REM sleep, so serotonin acts to promote arousal rather than to generate sleep. Their neurons have connections locally throughout the brainstem, while also projecting upward to the thalamus, hypothalamus, limbic system and cerebral cortex. Fibers transmitted downwards to the spinal cord are believed to inhibit sensory input such as pain signals. During REM sleep, the pons and medulla relax the limbs, preventing movement and thus ensuring we do not act out our dreams.

Thalamus

The thalamusthalamus plays a key role during REM sleep by transmitting glutamatergic sensory information to the cerebral cortex, contributing to the vivid nature of dreams. Specifically, the thalamic nuclei with excitatory projections towards the cerebral cortex are the midline and intralaminar nuclei. These nuclei consist of thalamocortical glutamatergic neurons responsible for tonic firing during REM. Relay nuclei such as the Lateral Geniculate Nucleus (LGN) and Medial Geniculate Nucleus (MGN) also remain active during REM stage for the provision of sensory information, though the depolarization of the cortex derives from the medial and intralaminar nuclei.

Pineal Gland

The pineal gland, under signals from the SCN, produces melatonin, a hormone that promotes sleep and regulates the sleep-wake cycle.

Basal Forebrain

The basal forebrain is part of the ascending arousal system and projects to the cerebral cortex to promote wakefulness. During waking, adenosine accumulates as a byproduct of energy metabolism and acts on the basal forebrain, building the sleep pressure that counteracts these arousal signals.

Amygdala

Lastly, the amygdala, responsible for processing emotions, becomes highly active during REM sleep, reflecting its role in emotional regulation and dream content.

Promotion of sleep

The key mediators promoting sleep are melatonin, gamma-aminobutyric acid (GABA), and adenosine.

Melatonin, often referred to as the “sleep hormone”, is produced by the pineal gland and serves a crucial role in regulating the sleep-wake cycle. The circadian rhythm is influenced by natural light, particularly blue light from the sun, which signals the brain to regulate melatonin production. Melatonin levels decrease in the morning, helping maintain wakefulness during the day and gradually increase in the evening to prepare the body for sleep. Melatonin is best known for promoting sleep and inhibiting wakefulness-promoting signals.

GABA serves as the primary inhibitory neurotransmitter of the central nervous system. By binding to GABA-A receptors in the brain, it reduces neuronal activity, facilitating the onset of sleep. Sleep-promoting neurons located in the anterior hypothalamus release GABA, which inhibits wake-promoting regions in both the hypothalamus and brainstem, thereby fostering a transition into sleep.

Adenosine is a neuromodulator that builds up during wakefulness, promotes drowsiness and counteracts wakefulness-promoting signals.

Inhibition of sleep

The key mediators of the inhibition of sleep are neurochemicals such as acetylcholine (ACh), norepinephrine, serotonin, histamine, and the hypocretin peptides.

ACh peaks during waking and REM sleep and decreases in NREM sleep.

Serotonin, from the dorsal raphe nucleus, and norepinephrine, from the locus coeruleus, promote arousal.

Norepinephrine inhibits REM sleep and interacts with other regions like the thalamus and hypothalamus.

Histamine, from the tuberomammillary nucleus, supports alertness whereas hypocretin projects to all major regions that regulate arousal, ensuring coordination of the wake-promoting mechanism.

The sleep-promoting and wake-promoting systems mutually inhibit each other, functioning as a flip-flop switch that ensures stable transitions between sleep and wakefulness.

Sleep stages are essential for the brain and body to recover and develop. It is crucial to obtain both deep sleep as well as REM sleep. Failure to achieve that can lead to significant effects on cognitive function, emotional regulation, and physical health. Frequent disruptions during lighter sleep stages, such as in sleep apnea, can prevent proper progression into deeper stages. Similarly, individuals with insomnia may not achieve enough total sleep to spend adequate time in each stage, further impacting overall well being.

Humans spend a third of their lives asleep, which amounts to decades dedicated to this intricate process. Understanding sleep and its physiological mechanisms gives the opportunity to enhance sleep quality, reduce health risks and improve well-being.