Sleep onset
Encyclopedia
Sleep onset is the transition from wakefulness into sleep. Sleep onset usually transmits into non-rapid eye movement sleep (NREM sleep) but in certain situations like narcolepsy
, it is possible to transmit from wakefulness directly into rapid eye movement sleep (REM sleep). It consists of a long neural pathway that extends from the retinal photoreceptor in the eye to the hypothalamus
.
and attacked the part of the brain that regulates sleep, influenced Europe and North America. Although the virus that caused this disorder was never identified, the psychiatrist and neurologist Constantin von Economo
, decided to study this disease and identified key component in the sleep-wake regulation. He identified the pathways that regulated wakefulness and sleep onset by studying the parts of the brain that were affected by the disease and the consequences it had on the circadian rhythm
. He stated that the pathways that regulated sleep onset are located in between the brain stem and the basal forebrain
. His discoveries were not appreciated until the last two decades of the 20th century when the pathways of sleep onset were found to reside in the exact place that Constantin von Economo
stated.
and the basal forebrain
, and throughout the cerebral cortex
. The cell group involved in the first pathway is an acetylcholine
-producing cell group called pedunculopontine and laterodorsal tegmental nucleus
(PPT/LDT). These neurons play a crucial role in bridging information in between the thalamus and the cerebral cortex. These neurons have high activation during wakefulness and during REM sleep and a low activation during NREM sleep. The second branch originates from monoaminorgenic neurons. These neurons are located in the locus coeruleus, dorsal and median raphe nuclei
, ventral periaqueductal grey matter, and tuberomammillary nucleus
. Each group produces a different neurotransmitter. The neurons in the locus coeruleus produce noradrenaline, as fore the neurons in the dorsal and median raphe nuclei
, ventral periaqueductal grey matter, and tuberomammillary nucleus
produce serotonin, dopamine and histamine respectively. They then project onto the hypothalamic peptidergic neurons, which contain melanin-concentrated hormones or orexin
, and basal forebrain neurons which contain GABA
and acetylcholine
. These neurons then project onto the cerebral cortex
. It has also been discovered that lesions to this part of the brain cause prolonged sleep or may produce coma.
Sleep onset is induced by sleep-promoting neurons, located in the ventrolateral preoptic nucleus
(VLPO). The sleep-promoting neurons are believed to project GABA
type A and galanin
, two known inhibitory neurotransmitters, to arousal-promoting neurons, such as histaminergic, serotonergic, orexinergic, noradrenergic, and cholinergic neurons (neurons mentioned above). Therefore it is believed that the activation of sleep-promoting neurons causes the inhibition of arousal-promoting neurons, which leads to sleep. Evidence has shown that during the sleep-wake cycle, the discharges of the sleep-promoting neurons and the arousal-promoting neurons have reciprocal discharges, and that during NREM sleep GABA
receptors increase in the arousal-promoting neurons. This had lead some to believe that the increase of GABA
receptors in the arousal-promoting neurons is another pathway of inducing sleep.
It is also known that the sleep-promoting neurons also receive input from the neurons that they inhibit. For example it is known that the monoaminorgic system inhibits VLPO neurons through serotonin
and noradrenaline. This suggests that the process of sleep onset is a feedback loop with circuits running in both directions. This is called a flip flop switch.
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
, it is possible to transmit from wakefulness directly into rapid eye movement sleep (REM sleep). It consists of a long neural pathway that extends from the retinal photoreceptor in the eye to the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
.
History
During the 1920s an obscure disorder that caused encephalitisEncephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
and attacked the part of the brain that regulates sleep, influenced Europe and North America. Although the virus that caused this disorder was never identified, the psychiatrist and neurologist Constantin von Economo
Constantin von Economo
Constantin Freiherr von Economo was a Romanian psychiatrist and neurologist of Greek origin. He is mostly known for his discovery of encephalitis lethargica and his atlas of cytoarchitectonics.- Youth and schooling :Constantin Freiherr Economo von San Serff was born in Brăila, Romania, to Greek...
, decided to study this disease and identified key component in the sleep-wake regulation. He identified the pathways that regulated wakefulness and sleep onset by studying the parts of the brain that were affected by the disease and the consequences it had on the circadian rhythm
Circadian rhythm
A circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...
. He stated that the pathways that regulated sleep onset are located in between the brain stem and the basal forebrain
Basal forebrain
The basal forebrain is a collection of structures located ventrally to the striatum. It is considered to be the major cholinergic output of the central nervous system . It includes a group of structures that lie near the bottom of the front of the brain, including the nucleus basalis, diagonal band...
. His discoveries were not appreciated until the last two decades of the 20th century when the pathways of sleep onset were found to reside in the exact place that Constantin von Economo
Constantin von Economo
Constantin Freiherr von Economo was a Romanian psychiatrist and neurologist of Greek origin. He is mostly known for his discovery of encephalitis lethargica and his atlas of cytoarchitectonics.- Youth and schooling :Constantin Freiherr Economo von San Serff was born in Brăila, Romania, to Greek...
stated.
Physiological overview
Von Economo, in his studies, noticed that lesions in the connection between the midbrain and the diencephalon caused prolonged sleepiness and therefore proposed the idea of an ascending arousal system. During the past few decades major ascending pathways have been discovered with located neurons and respective neurotransmitters. This pathway divides into two branches: one that ascends to the thalamus and activates the thalamus relay neurons, and another one that activates neurons in the lateral part of the hypothalamusHypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
and the basal forebrain
Basal forebrain
The basal forebrain is a collection of structures located ventrally to the striatum. It is considered to be the major cholinergic output of the central nervous system . It includes a group of structures that lie near the bottom of the front of the brain, including the nucleus basalis, diagonal band...
, and throughout the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
. The cell group involved in the first pathway is an acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
-producing cell group called pedunculopontine and laterodorsal tegmental nucleus
Laterodorsal tegmental nucleus
The laterodorsal tegmental nucleus is a nucleus situated in the brainstem, spanning the midbrain tegmentum and the pontine tegmentum...
(PPT/LDT). These neurons play a crucial role in bridging information in between the thalamus and the cerebral cortex. These neurons have high activation during wakefulness and during REM sleep and a low activation during NREM sleep. The second branch originates from monoaminorgenic neurons. These neurons are located in the locus coeruleus, dorsal and median raphe nuclei
Raphe nuclei
The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. Their main function is to release serotonin to the rest of the brain...
, ventral periaqueductal grey matter, and tuberomammillary nucleus
Tuberomammillary nucleus
The tuberomammillary nucleus is a subnucleus of the posterior third of the hypothalamus. It consists of, largely, histaminergic neurons and is involved with the control of arousal, sleep and circadian rhythm....
. Each group produces a different neurotransmitter. The neurons in the locus coeruleus produce noradrenaline, as fore the neurons in the dorsal and median raphe nuclei
Raphe nuclei
The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. Their main function is to release serotonin to the rest of the brain...
, ventral periaqueductal grey matter, and tuberomammillary nucleus
Tuberomammillary nucleus
The tuberomammillary nucleus is a subnucleus of the posterior third of the hypothalamus. It consists of, largely, histaminergic neurons and is involved with the control of arousal, sleep and circadian rhythm....
produce serotonin, dopamine and histamine respectively. They then project onto the hypothalamic peptidergic neurons, which contain melanin-concentrated hormones or orexin
Orexin
Orexins, also called hypocretins, are the common names given to a pair of excitatory neuropeptide hormones that were simultaneously discovered by two groups of researchers in rat brains....
, and basal forebrain neurons which contain GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
and acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
. These neurons then project onto the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
. It has also been discovered that lesions to this part of the brain cause prolonged sleep or may produce coma.
Sleep onset is induced by sleep-promoting neurons, located in the ventrolateral preoptic nucleus
Ventrolateral preoptic nucleus
The ventrolateral preoptic nucleus is a group of neurons in the hypothalamus. They are primarily active during Non-rapid eye movement sleep, and inhibit other neurons that are involved in wakefulness...
(VLPO). The sleep-promoting neurons are believed to project GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
type A and galanin
Galanin
Galanin is a neuropeptide encoded by the GAL gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors....
, two known inhibitory neurotransmitters, to arousal-promoting neurons, such as histaminergic, serotonergic, orexinergic, noradrenergic, and cholinergic neurons (neurons mentioned above). Therefore it is believed that the activation of sleep-promoting neurons causes the inhibition of arousal-promoting neurons, which leads to sleep. Evidence has shown that during the sleep-wake cycle, the discharges of the sleep-promoting neurons and the arousal-promoting neurons have reciprocal discharges, and that during NREM sleep GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
receptors increase in the arousal-promoting neurons. This had lead some to believe that the increase of GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
receptors in the arousal-promoting neurons is another pathway of inducing sleep.
It is also known that the sleep-promoting neurons also receive input from the neurons that they inhibit. For example it is known that the monoaminorgic system inhibits VLPO neurons through serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
and noradrenaline. This suggests that the process of sleep onset is a feedback loop with circuits running in both directions. This is called a flip flop switch.