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Encyclopedia > Raphe nuclei

The raphe nuclei (Latin for 'the bit in a fold or seam') is a moderately sized cluster of nuclei found in the brain stem, and releases serotonin to the rest of the brain. Selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to act at these nuclei. The brain stem is the stalk of the brain below the cerebral hemispheres. ... Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesised in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract. ... In the anatomy of animals, the brain, or encephalon, is the supervisory center of the nervous system. ... Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants. ... An antidepressant is a medication used primarily in the treatment of clinical depression. ...

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Raphe nuclei

The raphe nuclei are traditionally considered to be the medial portion of the reticular formation and have a vast impact upon the central nervous system. These serotonergic cells appear as a ridge of cells in the center and most medial portion of the brain stem. The raphe nuclei have been of particular interest to neurologists and psychologists, as they are the main effectors of serotonin in the brain. Reticular formation is a part of the brain which is involved in stereotypical actions, such as walking, sleeping, and lying down. ...

This diagram illustrates the projections of the raphe nuclei, though it does not show the proper indivudual nuclei, this is a good guide to their serotonergic projections

This monoamine, also called 5-HT, seems to be the culprit in many of our modern psycho-pharmaceutical problems, such as anorexia, depression, and sleep disorders. Arguably, it is not the sole culprit in the aforementioned disorders, but it is the area that the pharmacologists know how to affect in the best manner. It is important to note that pharmacology traditionally affects global serotonin levels, while the actions of the raphe nuclei are dependent on the complex interplay between nuclei. The 8 raphe nuclei receive afferent connections from some of the most fascinating spots in the brain, only to project back to them and alter their processes. Image File history File links Download high resolution version (800x851, 166 KB) File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ... In biochemistry, monoamines are a group of organic compounds containing only one amino group. ... Serotonin (5_hydroxytryptamine, or 5_HT) is a monoamine neurotransmitter synthesised in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract. ...


In order from caudal to rostral, the Raphe nuclei are known as the nucleus raphe obscurus, the raphe magnus, the raphe pontis, the raphe pallidus, the nucleus centralis superior, nucleus raphe dorsalis, nuclei linearis intermedius and linearis rostralis. Some scientists chose to groups to linearis nuclei into one nucleus, shrinking the number of raphe to seven. All of these nuclei have fascinating interactions with almost every pertinent portion of the brain, but only a few of them have specifically independent interaction worth exploring in their own right. These select nuclei are discussed as follows. In zootomy, several terms are used to describe the location of organs and other structures in the body of bilateral animals. ... In zootomy, several terms are used to describe the location of organs and other structures in the body of bilateral animals. ...


Overall, the caudal raphe nuclei, including the raphe magnus, pallidus and raphe obscurus, all project towards the spinal cord and brain stem. The more rostral nuclei, including the raphe pontis, centralis (also called median), dorsal, tend to project towards the brain areas of higher function.

Serotonergic Innervation in Rat Brain, taken from Kandel et. al. B1-3 = magnus, pallidus, obscurus. B4-9 = pontis, median, dorsal, both linnearis and others. HF= hippocampal formation. H= hypothalamus. Th=thalamus. CD = Caudate.

Image File history File links Download high resolution version (1437x813, 341 KB) File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ...

The Nucleus Raphe Obscurus

The nucleus raphe obscurus, despite the implications of its name, has some very specific functions and connections of afferent and efferent nature. The raphe obscurus projects to the cerebellar lobes VI and VII and to crus II along with the nucleus raphe pontis (Brodal, A. Neurological Anatomy in relation to Clinical Medication 3rd ed. Oxford Press. 1981). This so called obscure nucleus has also been implicated in the modulation of the hypoglossal nerve. It has been observed that the ablation of this nucleus causes a change in the firing pattern in the XII nerve (Peever JH, Necakov A, Duffin Nucleus raphé obscurus modulates hypoglossal output of neonatal rat in vitro transverse brain stem slices. J. Journal of Appl Physiol. 2001 Jan;90(1):269-79). In addition, the raphe obscurus mediates expiration via the inhibitory effect of serotonin and depresses periodic synaptic potentials (Lalley PM, Benacka R, Bischoff AM, Richter DW, Nucleus raphe obscurus evokes 5-HT-1A receptor-mediated modulation of respiratory neurons. Brain Research Volume 747, Issue 1 , 30 January 1997, Pages 156-159). It has also been shown that this nucleus stimulates gastrointestinal motor function, microinjections of 5-HT into the n.r. obscurus increase gastric movement (Krowicki, ZK and Hornby, PJ. Serotonin microinjected into the nucleus raphe obscurus increases intragastric pressure in the rat via a vagally mediated pathway. Pharmacology and Experimental Therapeutics. Volume 265, Issue 1, pp. 468-476, 04/01/1993).


The Nucleus Raphe Magnus

The nucleus raphe magnus, located directly rostral to the raphe obscurus, is afferently stimulated from axons in the spinal cord and cerebellum. This makes the magnus a likely candidate for part of the motor system; however, it seems to participate in the endogenous analgesia system. The magnus receives descending afferents from the periaqueductal gray, the paraventricular hypothalamic nucleus, central nucleus of the amygdala, lateral hypothalamic area, parvocellular reticular nucleus and the prelimbic, infralimbic, medial and lateral precentral cortices (Hermann, Dirk M. et al. Afferent projections to the rat nuclei raphe magnus, raphe pallidus and reticularis gigantocellularis pars demonstrated by iontophoretic application of choleratoxin (subunit b). Journal of Chemical Neuroanatomy Volume 13, Issue 1 , June 1997, Pages 1-21). All of these brain areas influence the main function of the raphe magnus. The main function of the magnus is mostly pain mediation; in fact it sends projections to the dorsal horn of the spinal cord to directly inhibit pain. The periaquiductal gray, the epicenter of analgesia, sends efferent connections to the nucleus raphe magnus in when it is stimulated by opiates (endogenous or otherwise). Electrical stimulation of the PAG produces analgesia, as well as administration of morphine to the PAG or n.r. magnus. The antinociceptic affects of electrical stimulation of the PAG can be blocked by administering naloxone, an opiate antagonist, to the n.r. magnus. All of this seems to indicate that the magnus is part of the endogenous opiate system, and acts to inhibit pain in the spinal cord. The spinal cord is a part of the vertebrate nervous system that is enclosed in and protected by the vertebral column (it passes through the spinal canal). ... Cerebellum (in blue) of the human brain For assistance with anatomical location terms, see Anatomical terms of location The cerebellum (literally little brain) is a brain region important for the integration of sensory perception with motor output. ... Structure of a skeletal muscle Muscle is one of the four tissue types. ... PeriAqueductal Gray (PAG) is the tegmental gray matter that is located around the cerebral aqueduct; it plays a role in the supression of pain and in defensive behavior. ... Location of the amygdala in the human brain Located in the brains medial temporal lobe, the almond-shaped amygdala (in Latin, corpus amygdaloideum) is believed to play a key role in the emotions. ... For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... Naloxone is a drug used to counter the effects of overdosing on opioids such as heroin and morphine. ... The antagonist is the character (or group of characters) of a story who represents the opposition against which the heroes and/or protagonists must contend. ...


The Nucleus Centralis Superior

The nucleus centralis superior is composed of polygonal, fusiform and pyriform neurons and exists rostral to the nucleus raphe pontis. One fascinating trait of the NCS is its inhibition by lysergic acid diethylamide and psilocin, two serotonin antagonist hallucinogens. The inactivation of the nucleus centralis superior via LSD produces a dose dependent inactivation in the NCS, but not in the raphe pallidus. The free moving cats, in which this was discovered, exhibited dose dependent behavioral changes (Trulson, M.E., Preussler DW and Trulson V.M. Differential effects of hallucinogenic drugs on the activity of serotonin-containing neurons in the nucleus centralis superior and nucleus raphe pallidus in freely moving cats. American Society for Pharmacology and Experimental Therapeutics Volume 228, Issue 1, pp. 94-102, 01/01/1984). LSD blotter paper D-Lysergic Acid Diethylamide, commonly called acid, LSD, or LSD-25, is a powerful semisynthetic hallucinogen and psychedelic entheogen. ... Psilocin is a mushroom alkaloid and derivative of the psychedelic hallucinogenic drug psilocybin. ... Hallucinogenic drugs or hallucinogens are drugs that can alter sensory perceptions, elicit alternate states of consciousness, or cause hallucinations. ...


The Nucleus Raphe Dorsalis

The nucleus raphe dorsalis is rich in 5-HT1a autoreceptors and is therefore a target of serotonin specific reuptake inhibitors, or SSRI’s. This nucleus is composed of small, medium and large cells, oddly enough it has been shown that the large cells contain norepinephrine (Steinbusch HW, Nieuwenhuys R, Verhofstad AA, Van der Kooy D. The nucleus raphe dorsalis of the rat and its projection upon the caudatoputamen. A combined cytoarchitectonic, immunohistochemical and retrograde transport study. Journal of Physiology (Paris). 1981;77(2-3):157-74). This is unusual because the raphe nuclei have traditionally been thought of as specifically serotonergic, and to have non-serotonin related neurons comes as quite a surprise. Ten percent of the axons from the nucleus raphe dorsalis have been shown to project to the amygdala (Ma QP, Yin GF, Ai MK, Han JS. Serotonergic projections from the nucleus raphe dorsalis to the amygdala in the rat. Neurosci Lett. 1991 Dec 16;134(1):21-4), while only medium cells seem to project to the caudate and putamen (Steinbusch HW, Nieuwenhuys R, Verhofstad AA, Van der Kooy D. The nucleus raphe dorsalis of the rat and its projection upon the caudatoputamen. A combined cytoarchitectonic, immunohistochemical and retrograde transport study. Journal of Physiology (Paris). 1981;77(2-3):157-74). SSRI is an acronym that stands for several things: It is a class of antidepressants called selective serotonin reuptake inhibitor SSRI also is used as the stock symbol for Silver Standard Resources Inc. ... Norepinephrine, known as noradrenaline outside the USA, is a catecholamine and a phenethylamine with chemical formula C8H11NO3. ... Location of the amygdala in the human brain Located in the brains medial temporal lobe, the almond-shaped amygdala (in Latin, corpus amygdaloideum) is believed to play a key role in the emotions. ... This article is about retrograde motion. ...


The nucleus raphe dorsalis has also been implicated in naloxone induced morphine withdrawl. It is known that endogenous opiate receptors exist on the nucleus raphe dorsalis, and that it is a focal point as an ascending and descending regulator. Pourshanazari et al showed in their 2000 paper that electrical stimulation of the nucleus raphe dorsalis can partially alleviate morphine withdrawl symptoms via electrical stimulation of the raphe nucleus in question (Pourshanazari, A.A. ; Alaei ; Rafati ; Effects of Electrical Stimulation of Nucleus Raphe Dorsalis on initiation of morphine self administration in rats. Medical Journal of Islamic Academy of Sciences 13:2, 63-67, 2000). These are fascinating results; however no control was provided for the spread of electrical charge to other parts of the brain stem. It is quite possible that the charge spread to the nucleus raphe magnus and induced analgesia upon the rats. Knowing that the spread of charge across such a short area is very plausible, as is an alternate connection to the raphe magnus, these results could be called into question. Wu M.F. et al. studied the raphe dorsalis as it pertained to narcolepsy, this is logical, as the raphe nuclei have been known to play a role in the sleep/wake cycle. Cataplexy is the symptom of narcolepsy when full awareness of the environment is maintained, but all muscle tone is lost. This has thought to be a dissociation of what normally happens during REM sleep, when all muscle tone is lost except for the eyes. The raphe dorsalis have been known to project to the lateral hypothalamus, along with the locus coeruleus and the tuberomammillary nucleus. The neurotransmitters of these three aforementioned nuclei, which project to the lateral hypothalamus, are serotonin, Norepinephrine and histamine respectively. These neurotransmitters are fully active during waking hours, partially active during non-REM sleep, and have almost ceased during REM sleep. In cats with pontine lesions, their normal atonia is not present, the raphe dorsalis is fully active, as opposed to the cessation of action under normal conditions. A muscle relaxant, known as Mephenesin, reduces to activity of the dorsal nucleus, as well as microinjections of carbachol (which induces atonia while awake) (Wu et al. Activity of Dorsal raphe cells across the sleep-waking cycle during cataplexy in narcoleptic dogs. Journal of Physiology. 2004 Jan 1;554(Pt 1):202-15). Morphine (INN), the principal active agent in opium, is a powerful opioid analgesic drug. ... Narcolepsy is a neurological condition characterized by severe fatigue, irresistible episodes of sleep and general sleep disorder. ... Categories: Possible copyright violations ... retarded or summat that yatsey says ... In the anatomy of mammals, the hypothalamus is a region of the brain located below the thalamus, forming the major portion of the ventral region of the diencephalon and functioning to regulate certain metabolic processes and other autonomic activities. ... The Locus ceruleus, also spelled locus coeruleus, (Latin for the blue bit) is a nucleus in the brain stem apparently responsible for the physiological reactions involved in stress and panic. ... Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesised in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract. ... Norepinephrine, known as noradrenaline outside the USA, is a catecholamine and a phenethylamine with chemical formula C8H11NO3. ... Histamine is a biogenic amine chemical involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. ... Clinical Info Chemistry and pharmacokinetics Carbachol is a choline ester and a positively charged quaternary ammonium compound. ...


The Nucleus Raphe Pallidus

The nucleus raphe pallidus receives afferent connections from the periaqueductal gray, the paraventricular hypothalamic nucleus, central nucleus of the amygdala, lateral hypothalamic area, and parvocellular reticular nucleus. Also, the pallidus receives afferents from the medial preoptic area, median preoptic nucleus and lateral paragigantocellular reticular nuclei (Hermann, Dirk M. et al. Afferent projections to the rat nuclei raphe magnus, raphe pallidus and reticularis gigantocellularis pars demonstrated by iontophoretic application of choleratoxin (subunit b). Journal of Chemical Neuroanatomy Volume 13, Issue 1 , June 1997, Pages 1-21). The pallidus has recently been shown to be involved in the activation of a fever as an immunoreaction. It has been implied that the preoptic area is constantly inhibiting the raphe pallidus, especially the rostral portion, with GABA. When the preoptic area receives immune signals from the body, the inhibition stops and the rostral portion of the raphe pallidus excites the intermediolateral cell column, which induces a fever (Nakamura, Kazuhiro et al. The Rostral Raphe Pallidus Nucleus Mediates Pyrogenic Transmission from the Preoptic Area. The Journal of Neuroscience, June 1, 2002, 22(11):4600-4610). The raphe pallidus has also been known to mediate the tachycardia response, an extremely high heart rate known to be incited by emotional or psychological stress. Microinjections of a GABA-a antagonist into the raphe pallidus, induces an increased heart rate. Conversely, microinjections of muscimol, a GABA-a agonist, inhibit tachycardia in rats under air-stress stimuli (Zaretsky, Dmitry V. et al. Microinjection of muscimol into raphe pallidus suppresses tachycardia associated with air stress in conscious rats. Journal of Physiology (2003), 546.1, pp. 243-250 © Copyright 2003). In both of these cases, GABA is mediating two different sympathetic responses, so clearly the nucleus raphe pallidus is a far more a complex nucleus than previously thought. PeriAqueductal Gray (PAG) is the tegmental gray matter that is located around the cerebral aqueduct; it plays a role in the supression of pain and in defensive behavior. ... Location of the amygdala in the human brain Located in the brains medial temporal lobe, the almond-shaped amygdala (in Latin, corpus amygdaloideum) is believed to play a key role in the emotions. ... Chemical structure of GABA Gamma-aminobutyric acid (GABA) is a neurotransmitter in widely divergent species. ... Agonists An agonist is a substance that binds to a receptor and triggers a response by the cell. ...



--Reid 00:52, 14 July 2005 (UTC)


See also

The Locus ceruleus, also spelled locus coeruleus, (Latin for the blue bit) is a nucleus in the brain stem (inferior to the cerebellum in the caudal midbrain/rostral pons) apparently responsible for the physiological reactions involved in stress and panic. ... The substantia nigra (Latin for black substance) is a portion of the midbrain thought to be involved in certain aspects of movement and attention. ... The pedunculopontine nucleus (PPN) is located in the brainstem, caudal to the substantia nigra and adjacent to the superior cerebellar peduncle. ... Human brain image constructed from MRI data // Brain (neural tube) Brainstem (rhombencephalon),(mesencephalon) Rhombencephalon (hindbrain) Metencephalon pons fourth ventricle cerebellum cerebellar vermis cerebellar hemispheres anterior lobe posterior lobe flocculonodular lobe cerebellar nuclei fastigial nucleus globose nucleus emboliform nucleus dentate nucleus Myelencephalon medulla oblongata medullary pyramids Mesencephalon (midbrain) tectum inferior colliculi...

External links

  • "Higher brain function: Activation of the brain and levels of consciousness."

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