By Yolanda Smith, BPharm
The regulation of sleep is important to control the transition between being awake and sleep.
Sleep is an unconscious state, marked by immobility and reduced responsiveness, of which there are two broad stages: rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. The brain is active during REM sleep whereas brain goes through periods of synchronized neuronal activity during NREM sleep.
An individual begins with NREM sleep and then switches to REM sleep, which is when dreaming may occur. There is a continuous cycle during sleep as the individual switches between the two phases until the person wakes.
The regulation of wakefulness and sleep is not fully understood, but the main pathways as they are currently known are outlined below.
There are several neurotransmitters that are thought to be involved in the regulation of sleep and arousal in the brain. These include:
- GABA from the VLPO nucleus promotes sleep
- Norepinephrine from the LC nucleus promotes arousal and hinders sleep
- Serotonin from the Raphe nucleus promotes arousal and hinders sleep
- Histamine from the TMN nucleus promotes arousal and hinders sleep
- Orexin from the LHA nucleus releases orexin and hinders sleep
LC, Raphe and TMN are the arousal-promoting nuclei and make connections throughout the cerebral cortex. When they release the norepinephrine, serotonin and histamine neurotransmitters, the cerebral cortex becomes activated to promote wakefulness and prevent sleep.
The VLPO nuclei are responsible for the release of GABA the main inhibitory neurotransmitter in the brain. This makes inhibitory connections to the arousal-promoting nuclei, leading to the suspension of arousal systems and the promotion of NREM sleep. The sleep-promoting and arousal-promoting nuclei are in direct competition, which leads to fast and complete transitions between the sleep and awake state.
Orexin plays an important role in the sleep cycle and the LHA nucleus that makes excitatory connections is most active during arousal. Abnormalities of this neurotransmitter in the central nervous system have been linked to narcolepsy, a sleeping disorder.
Sleep is also regulated by suprachiasmatic nucleus (SCN) in the hypothalamus of the brain, which controls the circadian rhythms in the body.
The SCN detects light signals from the surrounding environment via the optic nerve and responds through various processes, such as triggering the release of certain sleep-regulating hormones.
The eyes are exposed to intense light signals in the morning, causing the SCN to raise the body temperature, increase the production of the cortisol hormone, and delay the release of the melatonin hormone.
The SCN has an intrinsic pacemaker that continues to regulate the daily sleep cycle, even when individuals are confined to complete darkness without light cues for sleep.
In addition to normal physiological process, pharmaceutical compounds can also be used to regulate the sleep cycle.
Stimulants are compounds that increase arousal and wakefulness, which can be used in the management of condition involving excessive sleepiness during the day, such as for individuals with narcolepsy. Stimulants usually increase the activity of dopamine, norepinephrine and serotonin, such as amphetamine drugs and caffeine.
Hypnotics, on the other hand, increase the activity of GABA and increase sleepiness, which can be useful in the treatment of many sleep disorders to aid sleep. Examples of hypnotic drugs include benzodiazepines and other GABA potentiators.
The homeostatic regulation of sleep refers to the compensation of sleep by increasing sleep at the next opportunity, when an individual is deprived of sleep.
Last Updated: Mar 6, 2016