Ventrolateral preoptic nucleus

Last updated
Ventrolateral Preoptic Nucleus
Hypothalamus small.gif
The VLPO is located at the anterior of the hypothalamus. It is also called the intermediate nucleus of the preoptic area
Details
Part ofPreoptic nucleus
Identifiers
Acronym(s)VLPO or IPA
NeuroNames 3122
Anatomical terms of neuroanatomy

The ventrolateral preoptic nucleus (VLPO), also known as the intermediate nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain of humans and other animals. [1] [2] The brain's sleep-promoting nuclei (e.g., the VLPO, parafacial zone, nucleus accumbens core, and lateral hypothalamic MCH neurons), [3] [4] [5] [6] together with the ascending arousal system which includes components in the brainstem, hypothalamus and basal forebrain, are the interconnected neural systems which control states of arousal, sleep, and transitions between these two states. [1] [4] [5] The VLPO is active during sleep, particularly during non-rapid eye movement sleep (NREM sleep), [7] and releases inhibitory neurotransmitters, mainly GABA and galanin, which inhibit neurons of the ascending arousal system that are involved in wakefulness and arousal. [1] [8] The VLPO is in turn innervated by neurons from several components of the ascending arousal system. [9] The VLPO is activated by the endogenous sleep-promoting substances adenosine [10] [11] and prostaglandin D2. [12] The VLPO is inhibited during wakefulness by the arousal-inducing neurotransmitters norepinephrine and acetylcholine. [9] The role of the VLPO in sleep and wakefulness, and its association with sleep disorders – particularly insomnia and narcolepsy – is a growing area of neuroscience research.

Contents

Structure

At least 80% of neurons in the VLPO that project to the ascending arousal system are GABAergic (neurons that produce GABA). [13] In vitro studies in rats have shown that many neurons in the VLPO that are inhibited by norepinephrine or acetylcholine are multipolar triangular shaped cells with low threshold spikes. [9] These triangular multipolar neurons exist in two sub-populations in the VLPO:

As adenosine accumulates during wakefulness [11] it is likely that type 2 cells play a role in sleep induction.

The remaining third of neurons in the VLPO are excited by norepinephrine. Their role is unclear.

Function

Sleep/wakefulness

Schematic representation of the Flip-Flop Switch Hypothesis VLPO Flip-Flop Switch Hypothesis.png
Schematic representation of the Flip-Flop Switch Hypothesis

In the early 20th century, Constantin von Economo noted that humans who had encephalitis with lesions in the anterior hypothalamus had insomnia, and proposed a sleep-promoting influence from that area. [2] Animal studies in the mid-20th century in rats and cats confirmed that very large lesions in the preoptic area and basal forebrain resulted in insomnia [14] [15] but did not identify the cell group that was responsible. In 1996, Sherin and colleagues reported the presence of a cell group in the VLPO that expresses cFos (a protein often found in neurons that have recently been active) during sleep, and that these neurons contain the inhibitory neurotransmitters GABA and galanin. [13] [7] These same neurons were found to innervate components of the ascending arousal system, including the tuberomammillary nucleus (TMN) and other components of the lateral hypothalamus; the raphe nuclei; the locus coeruleus (LC); the pedunculopontine (PPT) and laterodorsal tegmental nuclei (LDT); and the parabrachial nucleus (PB). More recent studies using opto- or chemogenetic activation of VLPO neurons have confirmed that they promote sleep. [16]

The sleep-promoting effects of the VLPO neurons is thought to be due to release of GABA and possibly galanin that suppresses firing of arousal system neurons. As the VLPO is also inhibited by neurotransmitters released by components of the arousal systems, such as acetylcholine and norepinephrine, [9] a current theory has proposed that the VLPO and the arousal system form a "flip-flop" circuit. [1] [2] This term from electrical engineering denotes a circuit in which mutual inhibition means that each component of the circuit, as it turns on, turns the other off, resulting in rapid transitions from one state (wake or sleep) to the other, with minimal time in transition states. This theory has been used to create mathematical models that explain much of the wake-sleep behavior in animals, including in pathological states and responses to drugs. [1] [17] [18] Orexin neurons in the posterior lateral hypothalamus potentiate neurons in the ascending arousal system and help stabilize the brain in the waking state (and consolidated wakefulness, which builds up homeostatic sleep drive, helps stabilize the brain during later sleep). The loss of orexin neurons in the disorder narcolepsy destabilizes the wake-sleep switch, resulting in overwhelming sleep episodes during the waking day, as well as more frequent awakenings from sleep at night. [1]

Circadian rhythm

There is a strong circadian rhythm of sleep in mammals. The “master clock” for circadian rhythms in mammals is the suprachiasmatic nucleus (SCN). The SCN has little if any projection directly to the VLPO neurons. Instead, they project strongly to the adjacent subparaventricular zone, which in turn contains inhibitory GABAergic neurons that innervate the dorsomedial nucleus of the hypothalamus. [19] [20] Lesions of the dorsomedial nucleus almost completely eliminate the circadian rhythm of sleep. GABAergic neurons in the dorsomedial nucleus innervate the VLPO, and glutamatergic neurons innervate the lateral hypothalamus, suggesting that the dorsomedial nucleus mainly promotes wakefulness during the active period (daytime for humans). [19]

Clinical significance

Insomnia

Elderly human patients with more galanin neurons in their intermediate nucleus (the human equivalent of the VLPO galanin neurons in rodents) have better, more continuous sleep. A reduced number of VLPO neurons is associated with more fragmented sleep (more awakenings throughout the night). [21]

Lesions in the VLPO in rats results in 50-60% decrease in NREM sleep time and prolonged insomnia. [22] More recent research suggests that stress-induced insomnia could be due to an imbalance of input to arousal system and VLPO neurons. [23]

Sedative/hypnotic drugs

Many sedative/hypnotic drugs act by binding to and potentiating GABA-A receptors. These include older drugs such as ethanol, chloral hydrate and barbiturates, as well as newer benzodiazepines and "non-benzodiazepine" drugs (such as zolpidem, which bind to the same receptor but have a different chemical configuration), and even anesthetics such as propofol and isoflurane. As the VLPO inputs to the arousal system use this same receptor, these drugs at low doses essentially act by potentiating the VLPO, producing a sleepy state. Animal studies show that VLPO neurons show cFos activation after sedative doses of these drugs, [24] and that VLPO lesions produce resistance to their sedative effects. [25] However, at high doses that produce a surgical plane of anesthesia, these drugs have much more widespread inhibitory effects, that do not depend upon the VLPO. [26] Studies have shown that multiple sedative/hypnotic drugs that act by potentiating GABA-A receptors, including ethanol, chloral hydrate, propofol and gas anesthetics such as isoflurane, at sedative doses increase the activity of the VLPO neurons in mice. [27] This finding suggests that at relatively low sedative doses, these medications may have a common mechanism of action, which includes potentiating the firing of VLPO neurons. High doses used in surgical anesthesia, however, reduce activity of neurons throughout the nervous system.

Related Research Articles

Hypothalamus Area of the brain below the thalamus

The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond.

Orexin Neuropeptide that regulates arousal, wakefulness, and appetite.

Orexin, also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the sufferer experiences brief losses of muscle tone (cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.

Nucleus accumbens Region of the basal forebrain

The nucleus accumbens is a region in the basal forebrain rostral to the preoptic area of the hypothalamus. The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum. The ventral striatum and dorsal striatum collectively form the striatum, which is the main component of the basal ganglia. The dopaminergic neurons of the mesolimbic pathway project onto the GABAergic medium spiny neurons of the nucleus accumbens and olfactory tubercle. Each cerebral hemisphere has its own nucleus accumbens, which can be divided into two structures: the nucleus accumbens core and the nucleus accumbens shell. These substructures have different morphology and functions.

Wakefulness is a daily recurring brain state and state of consciousness in which an individual is conscious and engages in coherent cognitive and behavioral responses to the external world. Being awake is the opposite of the state of being asleep in which most external inputs to the brain are excluded from neural processing.

Suprachiasmatic nucleus Part of the brains hypothalamus

The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions in a 24-hour cycle. The mouse SCN contains approximately 20,000 neurons.

Ventral tegmental area Group of neurons on the floor of the midbrain

The ventral tegmental area (VTA), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and other dopamine pathways; it is widely implicated in the drug and natural reward circuitry of the brain. The VTA plays an important role in a number of processes, including reward cognition and orgasm, among others, as well as several psychiatric disorders. Neurons in the VTA project to numerous areas of the brain, ranging from the prefrontal cortex to the caudal brainstem and several regions in between.

Vasoactive intestinal peptide Hormone that affects blood pressure / heart rate

Vasoactive intestinal peptide, also known as vasoactive intestinal polypeptide or VIP, is a peptide hormone that is vasoactive in the intestine. VIP is a peptide of 28 amino acid residues that belongs to a glucagon/secretin superfamily, the ligand of class II G protein–coupled receptors. VIP is produced in many tissues of vertebrates including the gut, pancreas, and suprachiasmatic nuclei of the hypothalamus in the brain. VIP stimulates contractility in the heart, causes vasodilation, increases glycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gallbladder. In humans, the vasoactive intestinal peptide is encoded by the VIP gene.

Reticular formation Spinal trigeminal nucleus

The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. It is not anatomically well defined, because it includes neurons located in different parts of the brain. The neurons of the reticular formation make up a complex set of networks in the core of the brainstem that extend from the upper part of the midbrain to the lower part of the medulla oblongata. The reticular formation includes ascending pathways to the cortex in the ascending reticular activating system (ARAS) and descending pathways to the spinal cord via the reticulospinal tracts.

Slow-wave sleep

Slow-wave sleep (SWS), often referred to as deep sleep, consists of stage three of non-rapid eye movement sleep. Initially, SWS consisted of both Stage 3, which has 20–50 percent delta wave activity, and Stage 4, which has more than 50 percent delta wave activity.

The zona incerta (ZI) is a horizontally elongated region of gray matter in the subthalamus below the thalamus. Its connections project extensively over the brain from the cerebral cortex down into the spinal cord.

Basal forebrain

The basal forebrain structures are located in the forebrain to the front of and below the striatum. They include the ventral basal ganglia, nucleus basalis, diagonal band of Broca, substantia innominata, and the medial septal nucleus. These structures are important in the production of acetylcholine, which is then distributed widely throughout the brain. The basal forebrain is considered to be the major cholinergic output of the central nervous system (CNS) centred on the output of the nucleus basalis. The presence of non-cholinergic neurons projecting to the cortex have been found to act with the cholinergic neurons to dynamically modulate activity in the cortex.

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.

Dorsomedial hypothalamic nucleus

The dorsomedial hypothalamic nucleus is a nucleus of the hypothalamus. It is involved in feeding, drinking, body-weight regulation and circadian activity. More specifically, it is a necessary component for the expression of numerous behavioral and physiological circadian rhythms. The dorsomedial hypothalamic nucleus receives information from neurons and humors involved in feeding regulation, body weight and energy consumption, and then passes this information on to brain regions involved in sleep and wakefulness regulation, body temperature and corticosteroid secretion.

Lateral hypothalamus

The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity, and eating disorders.

Median preoptic nucleus Nucleus in the anterior hypothalamus

The median preoptic nucleus is located dorsal to the other three nuclei of the preoptic area of the anterior hypothalamus. The hypothalamus is located just beneath the thalamus, the main sensory relay station of the nervous system, and is considered part of the limbic system, which also includes structures such as the hippocampus and the amygdala. The hypothalamus is highly involved in maintaining homeostasis of the body, and the median preoptic nucleus is no exception, contributing to regulation of blood composition, body temperature, and non-REM sleep.

Galanin-like peptide (GALP) is a neuropeptide present in humans and other mammals. It is a 60-amino acid polypeptide produced in the arcuate nucleus of the hypothalamus and the posterior pituitary gland. It is involved in the regulation of appetite and may also have other roles such as in inflammation, sex behavior, and stress.

Sleep onset is the transition from wakefulness into sleep. Sleep onset usually transmits into non-rapid eye movement sleep but under certain circumstances it is possible to transit from wakefulness directly into rapid eye movement sleep.

Neuroscience of sleep Study of the neuroscientific and physiological basis of the nature of sleep

The neuroscience of sleep is the study of the neuroscientific and physiological basis of the nature of sleep and its functions. Traditionally, sleep has been studied as part of psychology and medicine. The study of sleep from a neuroscience perspective grew to prominence with advances in technology and proliferation of neuroscience research from the second half of the twentieth century.

The parabrachial nuclei, also known as the parabrachial complex, are a group of nuclei in the dorsolateral pons that surrounds the superior cerebellar peduncle as it enters the brainstem from the cerebellum. They are named from the Latin term for the superior cerebellar peduncle, the brachium conjunctivum. In the human brain, the expansion of the superior cerebellar peduncle expands the parabrachial nuclei, which form a thin strip of grey matter over most of the peduncle. The parabrachial nuclei are typically divided along the lines suggested by Baxter and Olszewski in humans, into a medial parabrachial nucleus and lateral parabrachial nucleus. These have in turn been subdivided into a dozen subnuclei: the superior, dorsal, ventral, internal, external and extreme lateral subnuclei; the lateral crescent and subparabrachial nucleus along the ventrolateral margin of the lateral parabrachial complex; and the medial and external medial subnuclei

The parafacial zone (PZ) is a brain structure located in the brainstem within the medulla oblongata believed to be heavily responsible for non-rapid eye movement (non-REM) sleep regulation, specifically for inducing slow-wave sleep.

References

  1. 1 2 3 4 5 6 Saper, Clifford B.; Fuller, Patrick M.; Pedersen, Nigel P.; Lu, Jun; Scammell, Thomas E. (2010). "Sleep State Switching". Neuron. 68 (6): 1023–1042. doi:10.1016/j.neuron.2010.11.032. PMC   3026325 . PMID   21172606.
  2. 1 2 3 Saper, Clifford B.; Scammell, Thomas E.; Lu, Jun (2005). "Hypothalamic regulation of sleep and circadian rhythms". Nature. 437 (7063): 1257–1263. doi:10.1038/nature04284. ISSN   0028-0836. PMID   16251950.
  3. ↑ Anaclet C, Ferrari L, Arrigoni E, Bass CE, Saper CB, Lu J, Fuller PM (September 2014). "The GABAergic parafacial zone is a medullary slow wave sleep-promoting center" (PDF). Nat. Neurosci. 17 (9): 1217–1224. doi:10.1038/nn.3789. PMC   4214681 . PMID   25129078. In the present study we show, for the first time, that activation of a delimited node of GABAergic neurons located in the medullary PZ can potently initiate SWS and cortical SWA in behaving animals. ... For now however it remains unclear if the PZ is interconnected with other sleep– and wake–promoting nodes beyond the wake–promoting PB. ... The intensity of cortical slow–wave–activity (SWA: 0.5–4Hz) during SWS is also widely accepted as a reliable indicator of sleep need ... In conclusion, in the present study we demonstrated that all polygraphic and neurobehavioral manifestation of SWS, including SWA, can be initiated in behaving animals by the selective activation of a delimited node of GABAergic medullary neurons.
  4. 1 2 Schwartz MD, Kilduff TS (December 2015). "The Neurobiology of Sleep and Wakefulness". The Psychiatric Clinics of North America. 38 (4): 615–644. doi:10.1016/j.psc.2015.07.002. PMC   4660253 . PMID   26600100. More recently, the medullary parafacial zone (PZ) adjacent to the facial nerve was identified as a sleep-promoting center on the basis of anatomical, electrophysiological and chemo- and optogenetic studies.23, 24 GABAergic PZ neurons inhibit glutamatergic parabrachial (PB) neurons that project to the BF,25 thereby promoting NREM sleep at the expense of wakefulness and REM sleep. ... Sleep is regulated by GABAergic populations in both the preoptic area and the brainstem; increasing evidence suggests a role for the melanin-concentrating hormone cells of the lateral hypothalamus and the parafacial zone of the brainstem
  5. 1 2 Brown RE, McKenna JT (June 2015). "Turning a Negative into a Positive: Ascending GABAergic Control of Cortical Activation and Arousal". Front. Neurol. 6: 135. doi:10.3389/fneur.2015.00135. PMC   4463930 . PMID   26124745. The sleep-promoting action of GABAergic neurons located in the preoptic hypothalamus (6–8) is now well-known and accepted (9). More recently, other groups of sleep-promoting GABAergic neurons in the lateral hypothalamus (melanin-concentrating hormone neurons) and brainstem [parafacial zone; (10)] have been identified.
  6. ↑ Oishi Y, Xu Q, Wang L, Zhang BJ, Takahashi K, Takata Y, Luo YJ, Cherasse Y, Schiffmann SN, de Kerchove d'Exaerde A, Urade Y, Qu WM, Huang ZL, Lazarus M (September 2017). "Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice". Nature Communications. 8 (1): 734. doi:10.1038/s41467-017-00781-4. PMC   5622037 . PMID   28963505. Here, we show that chemogenetic or optogenetic activation of excitatory adenosine A2A receptor-expressing indirect pathway neurons in the core region of the NAc strongly induces slow-wave sleep. Chemogenetic inhibition of the NAc indirect pathway neurons prevents the sleep induction, but does not affect the homoeostatic sleep rebound.
  7. 1 2 Sherin, J. E.; Shiromani, P. J.; McCarley, R. W.; Saper, C. B. (1996-01-12). "Activation of Ventrolateral Preoptic Neurons During Sleep". Science. 271 (5246): 216–219. doi:10.1126/science.271.5246.216. ISSN   0036-8075. PMID   8539624.
  8. ↑ Brown, Ritchie E.; Basheer, Radhika; McKenna, James T.; Strecker, Robert E.; McCarley, Robert W. (2012). "Control of Sleep and Wakefulness". Physiological Reviews. 92 (3): 1087–1187. doi:10.1152/physrev.00032.2011. ISSN   0031-9333. PMC   3621793 . PMID   22811426.
  9. 1 2 3 4 Gallopin, Thierry; Fort, Patrice; Eggermann, Emmanuel; Cauli, Bruno; Luppi, Pierre-Hervé; Rossier, Jean; Audinat, Etienne; Mühlethaler, Michel; Serafin, Mauro (2000). "Identification of sleep-promoting neurons in vitro". Nature. 404 (6781): 992–995. doi:10.1038/35010109. ISSN   0028-0836. PMID   10801127.
  10. ↑ Scammell, T.E; Gerashchenko, D.Y; Mochizuki, T; McCarthy, M.T; Estabrooke, I.V; Sears, C.A; Saper, C.B; Urade, Y; Hayaishi, O (2001). "An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons". Neuroscience. 107 (4): 653–663. doi:10.1016/s0306-4522(01)00383-9. ISSN   0306-4522.
  11. 1 2 Gallopin T (2005). "The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus". Neuroscience . 134 (4): 1377–1390. doi:10.1016/j.neuroscience.2005.05.045. PMID   16039802.
  12. ↑ Scammell T (1998). "Activation of ventrolateral preoptic neurons by the somnogen prostaglandin D2". PNAS . 95 (13): 7754–7759. doi:10.1073/pnas.95.13.7754. PMC   22747 . PMID   9636223.
  13. 1 2 Sherin J (1998). "Innervation of Histaminergic Tuberomammillary Neurons by GABAergic and Galaninergic Neurons in the Ventrolateral Preoptic Nucleus of the Rat". The Journal of Neuroscience . 18 (12): 4705–4721. doi: 10.1523/JNEUROSCI.18-12-04705.1998 . PMID   9614245.
  14. ↑ Nauta W (1946). "Hypothalamic regulation of sleep in rats". Journal of Neurophysiology . 9: 285–314. doi:10.1152/jn.1946.9.4.285. PMID   20991815.
  15. ↑ McGinty D (1968). "Sleep Suppression after Basal Forebrain Lesions in the Cat". Science . 160 (3833): 1253–1255. doi:10.1126/science.160.3833.1253. PMID   5689683.
  16. ↑ Kroeger, Daniel; Absi, Gianna; Gagliardi, Celia; Bandaru, Sathyajit S.; Madara, Joseph C.; Ferrari, Loris L.; Arrigoni, Elda; Münzberg, Heike; Scammell, Thomas E. (2018). "Galanin neurons in the ventrolateral preoptic area promote sleep and heat loss in mice". Nature Communications. 9 (1). doi:10.1038/s41467-018-06590-7. ISSN   2041-1723. PMC   6175893 . PMID   30297727.
  17. ↑ Phillips, A.J.K.; Robinson, P.A. (2007). "A Quantitative Model of Sleep-Wake Dynamics Based on the Physiology of the Brainstem Ascending Arousal System". Journal of Biological Rhythms. 22 (2): 167–179. doi:10.1177/0748730406297512. ISSN   0748-7304. PMID   17440218.
  18. ↑ Fulcher, Ben D.; Phillips, Andrew J. K.; Postnova, Svetlana; Robinson, Peter A. (2014). Mistlberger, Ralph E. (ed.). "A Physiologically Based Model of Orexinergic Stabilization of Sleep and Wake". PLoS ONE. 9 (3): e91982. doi:10.1371/journal.pone.0091982. ISSN   1932-6203. PMC   3961294 . PMID   24651580.
  19. 1 2 Chou, Thomas C.; Scammell, Thomas E.; Gooley, Joshua J.; Gaus, Stephanie E.; Saper, Clifford B.; Lu, Jun (2003). "Critical Role of Dorsomedial Hypothalamic Nucleus in a Wide Range of Behavioral Circadian Rhythms". The Journal of Neuroscience. 23 (33): 10691–10702. doi: 10.1523/jneurosci.23-33-10691.2003 . ISSN   0270-6474.
  20. ↑ Vujovic, Nina; Gooley, Joshua J.; Jhou, Thomas C.; Saper, Clifford B. (2015). "Projections from the subparaventricular zone define four channels of output from the circadian timing system: Projections from the SPZ". Journal of Comparative Neurology. 523 (18): 2714–2737. doi:10.1002/cne.23812. PMC   4607558 . PMID   26010698.
  21. ↑ Lim A (2014). "Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer's disease". Brain . 137 (Pt 10): 2847–61. doi:10.1093/brain/awu222. PMC   4163039 . PMID   25142380.
  22. ↑ Lu, Jun; Greco, Mary Ann; Shiromani, Priyattam; Saper, Clifford B. (2000). "Effect of Lesions of the Ventrolateral Preoptic Nucleus on NREM and REM Sleep". The Journal of Neuroscience. 20 (10): 3830–3842. doi: 10.1523/jneurosci.20-10-03830.2000 . ISSN   0270-6474.
  23. ↑ Cano, G.; Mochizuki, T.; Saper, C. B. (2008). "Neural Circuitry of Stress-Induced Insomnia in Rats". Journal of Neuroscience. 28 (40): 10167–10184. doi: 10.1523/JNEUROSCI.1809-08.2008 . ISSN   0270-6474.
  24. ↑ Lu, Jun; Nelson, Laura E.; Franks, Nick; Maze, Mervyn; Chamberlin, Nancy L.; Saper, Clifford B. (2008). "Role of endogenous sleep-wake and analgesic systems in anesthesia". The Journal of Comparative Neurology. 508 (4): 648–662. doi:10.1002/cne.21685. PMC   4924624 . PMID   18383504.
  25. ↑ Moore, Jason T.; Chen, Jingqiu; Han, Bo; Meng, Qing Cheng; Veasey, Sigrid C.; Beck, Sheryl G.; Kelz, Max B. (2012). "Direct Activation of Sleep-Promoting VLPO Neurons by Volatile Anesthetics Contributes to Anesthetic Hypnosis". Current Biology. 22 (21): 2008–2016. doi:10.1016/j.cub.2012.08.042. PMC   3628836 . PMID   23103189.
  26. ↑ Eikermann, Matthias; Vetrivelan, Ramalingam; Grosse-Sundrup, Martina; Henry, Mark E.; Hoffmann, Ulrike; Yokota, Shigefumi; Saper, Clifford B.; Chamberlin, Nancy L. (2011). "The ventrolateral preoptic nucleus is not required for isoflurane general anesthesia". Brain Research. 1426: 30–37. doi:10.1016/j.brainres.2011.10.018. PMC   3215917 . PMID   22041226.
  27. ↑ Moore J (2012). "Direct Activation of Sleep-Promoting VLPO Neurons by Volatile Anesthetics Contributes to Anesthetic Hypnosis". Current Biology . 22 (21): 2008–2016. doi:10.1016/j.cub.2012.08.042. PMC   3628836 . PMID   23103189.

Gallopin T, Luppi PH, Cauli B, Urade Y, Rossier J, Hayaishi O, Lambolez B, Fort P (2005). "The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus". Neuroscience. 134 (4): 1377–90. doi:10.1016/j.neuroscience.2005.05.045. PMID   16039802.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.