Raphe nuclei

The raphe nuclei (Greek: ῥαφή "seam"[1]) are a moderate-size cluster of nuclei
Raphe nuclei
found in the brain stem. Their main function is to release serotonin to the rest of
the brain.[2] Selective serotonin reuptake inhibitor (SSRI) antidepressants are
gets.[3]
believed to act in these nuclei, as well as at their tar

Contents
Anatomy
Nomenclature
Projections
Section of the medulla oblongata at
Function
about the middle of the olive. (Raphe
The raphe nuclei and the effects of ghrelin
nuclei not labeled, but 'raphe' labeled at
See also
left.)
References
Further reading

Anatomy
The raphe nuclei are traditionally considered to be the medial portion of the
reticular formation, and appear as a ridge of cells in the center and most medial
portion of the brain stem.
Horizontal cross section of the
In order from caudal to rostral, the raphe nuclei are known as the nucleus raphe brainstem at the lower pons. The raphe
obscurus, the nucleus raphe pallidus, the nucleus raphe magnus, the nucleus nucleus is labeled #18 in the middle.
raphe pontis, the median raphe nucleus, dorsal raphe nucleus, caudal linear Details
nucleus.[4] In the first systematic examination of the raphe nuclei, Taber et al..
Identifiers
(1960)[5] originally proposed the existence of two linear nuclei (nucleus linearis
Latin nuclei raphe
intermedius and nucleus linearis rostralis). This study was published before
techniques enabling the visualization of serotonin or the enzymes participating MeSH D011903
in its synthesis had been developed, as first demonstrated by Dahlström and NeuroLex ID Raphe Nuclei
Fuxe in 1964.[6] Later, it was revealed that of these two nuclei, only the former TA A14.1.04.257
(nucleus linearis intermedius, now known as the caudal linear nucleus), proved A14.1.04.318
to contain serotonin-producing neurons,[7] though both of them contain A14.1.05.402
dopaminergic neurons.[8] A14.1.05.601
In some works (e.g.[9]), researchers have grouped the nuclei lineares into one
A14.1.06.401
nucleus, the nucleus linearis, shrinking the number of raphe to seven, e.g., FMA 84017
NeuroNames makes the following ordering:[10] Anatomical terms of neuroanatomy

Raphe nuclei of medulla oblongata

Nucleus raphe obscurus

Nucleus raphe magnus
Nucleus pallidus
 Raphe nuclei of the pontine reticular formation

Nucleus raphe pontis

Nucleus centralis inferior
Raphe nuclei of the midbrain reticular formation

Nucleus centralis superior(median raphe nucleus)

Nucleus raphe dorsalis

Nomenclature
The Latin names commonly used for most of these nuclei are grammatically and orthographically incorrect. Latin grammar would
require to use the genitive case raphes ('of the seam') instead of the nominative case raphe ('seam') in these Latin expressions. The
main authority in anatomical names, Terminologia Anatomica uses for example nucleus raphes magnus[11] instead of the
grammatically incorrect nucleus raphe magnus. The spelling raphe/raphes however can also be contested as numerous
sources[12][13][14] indicate that raphe is an incorrect Latin rendering of the Ancient Greek word ῥαφή as the initial letter rho with
rough breathing (spiritus asper) is normally rendered as rh in Latin.[12] The edition of the Nomina Anatomica that was ratified in
Jena in 1935 used rhaphe instead of raphe.[15][16]

Projections
These nuclei interact with almost every pertinent portion of the brain, but only a few of them have specifically independent
interaction. These select nuclei are discussed as follows.

Overall, the caudal raphe nuclei, including the nucleus raphe magnus, nucleus raphe pallidus and nucleus raphe obscurus, all project
towards the spinal cord and brain stem. The more-rostral nuclei, including the nucleus raphe pontis, nucleus centralis superior (also
[17]
called median raphe nucleus) and nucleus raphe dorsalis project towards the brain areas of higher function

However, studies also show that numerous areas of the brain control the serotonergic neurons located in the nucleus raphe dorsalis,
including the orbital cortex, cingulate cortex, medial preoptic area, lateral preoptic area, and several areas of the hypothalamus. The
connection between these areas, particularly between the nucleus raphe dorsalis and the orbital cortices, is thought to have influences
on depression and obsessive compulsive disorderprognosis.[18]

Function
The raphe nuclei have a vast impact upon the central nervous system. Many of the
neurons in the nuclei (but not the majority) are serotonergic; i.e., contain serotonin, a
type of monoamine neurotransmitter and are modulated through fibrous pathways in
the midbrain.[19]

Projections from the raphe nuclei also terminate in the dorsal horn of spinal gray
matter where they regulate the release ofenkephalins, which inhibit pain sensation. Dopamine and serotonin pathways in
the brain
The raphe nuclei provide feedback to the suprachiasmatic nuclei (SCN), thus
contributing in circadian rhythms in animals. The SCN transmits to the raphe nuclei
via the dorsomedial hypothalamus nucleus altering serotonin levels for sleep/wake states. The raphe nuclei will then transmit
feedback to the SCN about the animal's vigilance and levels of alertness. This reciprocal feedback between the two structures
[20]
provides an adaptable yet stable basis of circadian rhythms.

The raphe nuclei and the effects of ghrelin

More recent studies of the Raphe Nuclei done with rats involve the effects of Ghrelin on the dorsal raphe nucleus. When
administered, larger doses of Ghrelin act centrally on the raphe nucleus, hippocampus, and amygdala which causes dramatic
increases in food intake, memory retention, and increases in anxiety. The effects of ghrelin are seen on the raphe nucleus as soon as
an hour after injection, suggesting rapid changes in the nucleus' structure. Changes also occur after 24 hours suggesting delayed
modifications as well.[21]

See also
Locus ceruleus
Substantia nigra
Pedunculopontine nucleus
List of regions in the human brain

References
1. Liddell, H.G. & Scott, R. (1940).A Greek-English Lexicon. revised and augmented throughout by Sir Henry Stuart
Jones. with the assistance of. Roderick McKenzie.Oxford: Clarendon Press.
2. George J. Siegel, ed. (1999)."Understanding the neuroanatomical organization of serotonergic cells in brain
provides insight into the functions of this neurotransmitter"(https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Sear
ch&db=books&doptcmdl=GenBookHL&term=raphe+AND+serotonin+release+AND+bnchm%5Bbook%5D+AND+160
428%5Buid%5D&rid=bnchm.section.946#949) . Basic Neurochemistry (https://www.ncbi.nlm.nih.gov/books/bv.fcgi?ri
d=bnchm). Bernard W. Agranoff, Stephen K. Fisher, R. Wayne Albers, Michael D. Uhler (Sixth ed.). Lippincott
Williams and Wilkins. ISBN 0-397-51820-X. "In 1964, Dahlstrom and Fuxe (discussed in [2]), using the Falck-Hillarp
technique of histofluorescence, observed that the majority of serotonergic soma are found in cell body groups, which
previously had been designated as the raphe nuclei. "
3. Briley, M; Moret, C (October 1993). "Neurobiological mechanisms involved in antidepressant therapies".Clin
Neuropharmacol. 16 (5): 387–400. doi:10.1097/00002826-199310000-00002(https://doi.org/10.1097%2F00002826-
199310000-00002). PMID 8221701 (https://www.ncbi.nlm.nih.gov/pubmed/8221701).
4. Törk, Istvan (1990). "Anatomy of the serotonergic system".Annals of the New York Academy of Sciences. 600: 12.
doi:10.1111/j.1749-6632.1990.tb16870.x(https://doi.org/10.1111%2Fj.1749-6632.1990.tb16870.x) . PMID 2252340
(https://www.ncbi.nlm.nih.gov/pubmed/2252340).
5. Taber, Elizabeth; Brodal, Alf; Walberg, Fred (1960). "The raphe nuclei of the brain stem in the cat. I. Normal
topography and cytoarchitecture and general discussion".J Comp Neurol. 114 (2): 161–187.
doi:10.1002/cne.901140205(https://doi.org/10.1002%2Fcne.901140205). PMID 13836517 (https://www.ncbi.nlm.ni
h.gov/pubmed/13836517).
6. Dahlström, Annica; Fuxe, Kjell (1964). "Evidence for the existence of monoamine-containing neurons in the central
nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons".
Acta Physiol Scand. 232
(Suppl): 1–55. PMID 14229500 (https://www.ncbi.nlm.nih.gov/pubmed/14229500).
7. Halliday, Glenda M.; Törk, Istvan (1989). "Serotonin-like immunoreactive cells and fibres in the rat ventromedial
mesencephalic tegmentum".Brain Res Bull. 22 (4): 727–9. PMID 2736398 (https://www.ncbi.nlm.nih.gov/pubmed/27
36398).
8. Ikemoto, Satoshi (2007)."Dopamine reward circuitry: two projection systems from the ventral midbrain to the
nucleus accumbens-olfactory tubercle complex"(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134972). Brain
Res Rev. 56 (1): 27–78. doi:10.1016/j.brainresrev.2007.05.004 (https://doi.org/10.1016%2Fj.brainresrev
.2007.05.00
4). PMC 2134972 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134972) . PMID 17574681 (https://www.ncbi.nl
m.nih.gov/pubmed/17574681).
9. Nieuwenhuys, Rudolf; Voogd, Jan; van Huijzen, Chris (2008). The human central nervous system(4 ed.). Berlin:
Springer. pp. 890, 893.
10. ancil-190 (http://braininfo.rprc.washington.edu/Scripts/ancilcentraldirectory
.aspx?ID=190) at NeuroNames
11. Federative Committee on Anatomical T
erminology (FCAT) (1998). Terminologia Anatomica. Stuttgart: Thieme
12. Hyrtl, J. (1880). Onomatologia Anatomica. Geschichte und Kritik der anatomischen Sprache der Gegenwart.
Wien:
Wilhelm Braumüller. K.K. Hof- und Universitätsbuchhändler.
13. Foster, F.D. (1891-1893). An illustrated medical dictionary. Being a dictionary of the technical terms used by writers
on medicine and the collateral sciences, in the Latin, English, French, and German languages. New York: D.
Appleton and Company.
14. Triepel, H. (1910). Die anatomischen Namen. Ihre Ableitung und Aussprache. Mit einem Anhang: Biographische
Notizen.(Dritte Auflage). Wiesbaden: Verlag J.F. Bergmann.
15. Kopsch, F. (1941). Die Nomina anatomica des Jahres 1895 (B.N.A.) nach der Buchstabenreihe geordnet und
gegenübergestellt den Nomina anatomica des Jahres 1935 (I.N.A.)(3. Auflage). Leipzig: Georg Thieme Verlag.
16. Stieve, H. (1949). Nomina Anatomica. Zusammengestellt von der im Jahre 1923 gewählten Nomenklatur -
Kommission, unter Berücksichtigung der V orschläge der Mitglieder der Anatomischen Gesellschaft, der Anatomical
Society of Great Britain and Ireland, sowie der American Association of Anatomists, überprüft und durch Beschluß
der Anatomischen Gesellschaft auf der T agung in Jena 1935 endgültig angenommen.(Vierte Auflage). Jena: Verlag
Gustav Fischer.
17. BilZ0r; Erowid (2005). "Figure 4. Diagram of the human brain showing the divergent serotonergic projections of the
raphe nuclei to both cortical and subcortical locations throughout the brain"
(http://www.erowid.org/psychoactives/ph
armacology/images/pharmacology_article2-4-med.png)(PNG). The Neuropharmacology of Hallucinogens: a
technical overview. Erowid Pharmacology Vaults. Retrieved 18 April 2006.
18. C. Peyron; J.M Petit; C. Rampon; M. Jouvet; P
.H. Luppi (1998). "Forebrain Afferants to the Rat Dorsal Raphe
Nucleus Demonstrated by Retrograde and Anterograde rTacing Methods" (http://ac.els-cdn.com/S03064522970026
86/1-s2.0-S0306452297002686-main.pdf?_tid=73fbf f06-d575-11e3-bf75-00000aacb35e&acdnat=1399418798_91a9
841e1f82ab68d665fe871439759f)(PDF). Neuroscience. 82 (2): 443–468. doi:10.1016/s0306-4522(97)00268-6(http
s://doi.org/10.1016%2Fs0306-4522%2897%2900268-6) .
19. Efrain C. Azmitia & Menahem Segal (2004)."An Autoradiographic Analysis of the Differential Ascending Projections
of the Dorsal and Median Raphe Nuclei in the Rat"(http://onlinelibrary.wiley.com/doi/10.1002/cne.901790311/abstrac
t;jsessionid=6388235C695A2662C3AE9DC4E0CB117B.f03t01?deniedAccessCustomisedMessage=&userIsAuthenti
cated=false). The Journal of Comparative Neurology. 179 (3): 641–667. doi:10.1002/cne.901790311(https://doi.org/
10.1002%2Fcne.901790311). PMID 565370 (https://www.ncbi.nlm.nih.gov/pubmed/565370).
20. J.M. Monti, ed. (2008)."Reciprocal connections between the suprachiasmatic nucleus and the midbrain raphe
nuclei: A putative role in the circadian control of behavioral states"(http://www.springerlink.com/content/p72n6176g4
067317). Serotonin and Sleep: Molecular, Functional and Clinical Aspects (http://www.springerlink.com/content/p72n
6176g4067317/). Samüel Deurveilher and Kazue Semba. Birkhäuser Basel.ISBN 978-3-7643-8560-6.
21. Valeria P Carlinia; Mariana M Varasa; Andrea B Cragnolinia; Helgi B Schiöthb; e Tresa N Scimonellia; Susana R de
Barioglio (2004). "Differential Role of the Hippocampus, amygdala, and Dorsal Raphe Nucleus in Regulating
Feeding, Memory, and Anxiety-like Behavioral Responses to Ghrelin"(http://su8bj7jh4j.scholar.serialssolutions.co
m/?sid=google&auinit=VP&aulast=Carlini&atitle=Dif ferential+role+of+the+hippocampus,+amygdala,+and+dorsal+rap
he+nucleus+in+regulating+feeding,+memory ,+and+anxiety-like+behavioral+responses+to+ghrelin&id=doi:10.1016/j.
bbrc.2003.11.150&title=Biochemical+and+biophysical+research+communications&volume=313&issue=3&date=200
4&spage=635&issn=0006-291X). Biochemical and Biophysical Research Communications . 313 (3): 635–641.
doi:10.1016/j.bbrc.2003.11.150(https://doi.org/10.1016%2Fj.bbrc.2003.11.150) .

Further reading
Currie, David (2005). "A Lecture, Higher Brain Function: Activation of the Brain and Levels of Consciousness". East
Tennessee State University. Retrieved 18 April 2006.
Sari, Youssef (October 2004)."Serotonin1B receptors: from protein to physiological function and behavior" .
Neuroscience & Biobehavioral Reviews. 28 (6): 565–582. doi:10.1016/j.neubiorev.2004.08.008. PMID 15527863.
Retrieved 2006-04-18.
McKittrick,, Christina; Carolineblanchard, D; Blanchard, R; McEwen, B; Sakai, R (August 1995). "Serotonin Receptor
Binding in a Colony Model of Chronic Social Stress". Biological Psychiatry. 37 (6): 383–393. doi:10.1016/0006-
3223(94)00152-S. PMID 7772647. Retrieved 2010-08-30.

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