Raphe Nuclei

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This page will be update by the 27th of Auj. Ninad Mehta

Basic Information

During the mid-nineteen century it was observed that the serum that was left after the clotting of the blood could constrict vascular smooth muscle so as to increase the vascular tone. It was later discovered that blood platelets were a source of this substance. Rapport and his collaborators[1] later isolated this compound and named it serotonin(5-hydrocytryptamine). Since the structure of 5-HT is hydrophilic and this would imply that I would not be able to pass through the blood-brain barrier and thus the presence of 5-HT in the blood suggested that it was produced in the brain. In 1964, Dahlstrom and Fuxe using the method of histoflurescence found that the majority of serotonergic soma was found in the midline of the brainstem. This locus had been designated as the raphe nuclei[2]. One fact that must be kept in mind is that not all the neurons in the raphe nuclei are serotonergic.

Schematic drawing depicting the location of the serotonergic cell body groups in a sagittal section of the rat central nervous system and their major projections. OT, olfactory tuberculum; Sept, septum; C. Put, nucleus caudate-putamen; G. Pal, globus pallidus; T, thalamus; H, habenula; S. Nigra, substantia nigra.[1] http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.figgrp.950


Traditional Dahlstrom and Fuxe described nine group of serotonin-containing cell bodies and they were designated B1 to B9. The figure shows the nine cell bodies and the region of the brain that they invigilate. The B1 to B4 are located in the midpons to caudal medulla. The largest group of serotonergic cells is the B7 . It is continuous with the B6 group of cells and they together from are called as the dorsal raphe nucleus. B8 is termed as median raphe nucleus(the nucleus central superior.) Group B9 is located in the ventrolateral tegmentum of the pons of the midbrain. The dorsal and the median raphe nuclei give rise to distinct projection in the forebrain region. Within this raphe the neurons are organized into groups that send axon to specific areas of the brain. The organized innervations of the fore brain structure by raphe neuron implies to the fact that the function of the neuron is dependent on their origin and terminal projection.

Some researchers use a different method of nomenclature for the Raphe nuclei. NeuroNames has shown a classification of the raphe nuclei into seven parts:-

Raphe nuclei of medulla:-

 Nucleus raphe obscures
 Nucleus raphe magnus
 Nucleus pallidus.

Raphe nuclei of the pontine reticular formation

 Pontine raphe nucleus
 Inferior central nucleus

Raphe nuclei of the Midbrain reticular formation

 Superior central nucleus
 Dorsal Raphe nucleus

Specification of the Neuron

As mentioned earlier the total number of the serotonergic neurons is really small. In Rats the number of neurons is around 20,000 out of some 1010 neurons. The Neurons are generated in the early stages of embryonic development. It has been commonly observed that a day after the generation of the neurons they can start the production of 5-HT[3]. The raphe neurons also start profuse axon tracts and project into many parts of the brain and the spinal cord. Based on the labeled 5-HT uptake experiments and immunohistochemical techniques difference in the raphe nuclei neurons have been observed.

The axons of the neurons from the median raphe nucleus, type M, have coarse large spherical varicosities while the ones from the dorsal raphe, type D, have very fine and small pleomorphic varicosities.

This is a simplified diagram of the D- and the M- type of raphe neurons. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=raphe%20nuclei&rid=bnchm.section.946#949

This model for possible interaction between serotonergic and GABAergic neuron in the raphe nuclei. Image Taken from :- The Pharmacology of the Neurochemical Transmission in the Midbrain Raphe Nuclei of the Rat, Curr Neuropharmacol. 2006 October; 4(4): 313–339.

The serotonergic neurons of the raphe nuclei exhibit spontaneous discharge activity of 1-5 spikes per second. [5] The activity of this neurons is controlled by three different events that take place in the nuclei. The events initially start of with the slow firing activity of 5-HT neurons, the autoinhibitry action of 5-HT and also by the signals provided by non-5-HT receptors. Both axon and Dendron’s act as the site for the 5-HT release. [6]. The non-5-HT neurons in the raphe nuclei are GABA-containing interneurons. The function of this neurons is to establish local connection with the 5-HT neurons. It has been observed that GABA inhibits serotonergic system as it reduces the turn-over rate of 5-HT in the raphe nuclei. [7]


Molecular profile

  • Neurotransmitter:Serotonin is a combination of the hydroxyl group in the 5 position of the indole nucleus and a primary amine nitrogen.[1] 5-HT is released from the serotonergic varicosities into the extra neuron place and not from the synaptic terminal boutons. The diffusion area of 5-HT is >20µm of the active receptor.[8]
The Structure of Serotonin and its related compounds http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.figgrp.948
  • Receptor:The receptor for the serotonin are the same as the for 5-HT and they are located on the cell membrane of the neurons. Most of the 5-HT receptor in the neurons are G-proteins. When the ligand binds to this receptor it will activate and intracellular second messenger cascade. Seven classes of Receptor are know in case of mice. The information of the receptor is given in the table.
doi:10.1038/nrn125. The original table shows a lot more information then what is displayed here



Serotonin plays an important role in the modulation of mood swings, anger, anxiety, aggression, body temperature, sleep, appetite, metabolism and sexuality. Serotonin is one of the major players in stimulating vomiting.

Researcher have found that mutation in the 5-HT2A receptor was much common in patients with major depression and suicidal tendencies. Studies on human patients groups have also shown that lower levels of serotonin leads to the shift of the behavior pattern to aggressiveness.

Gross and et al, have found that Serotonin 1A receptor acts during the development of a mice and leads to normal anxiety like behavior in adult mice. The knock – out of this receptor in these mice have shown higher levels of anxiety in the mice.[9] Groups of Researchers have also found that mice with defective serotonin receptors or 5-HT levels show deviations from the normal pattern of behavior in case of a maze experiment.

Serotonin has also been linked with SIDS ( sudden infant death syndrome). Lesurtel M. el al have shown that low levels of serotonin in mice brainstems that control heartbeat and breathing maybe one of the reasons for SIDS. Lately it has also been found that the serotonergic neurons in raphe have central respiratory chemoreceptos. It has also been proposed that the mid brain raphe neurons can sense the carbon dioxide. It is also believed that the raphe can induce anxiety, arousal or cerebrovascular modification so as to maintain the pH homeostasis.

Midbrain serotonergic neurons are closely associated with large arteries. Shown are confocal images of transverse midbrain slices after injecting arteries with fluorescent albumin (red) and performing immunohistochemistry for TPH (green). Note:- Severson C I, et al. Midbrain serotonergic neurons are central pH chemoreceptors


  1. Basic neurochemistry 3rd edition,edited by George J. Siegel ... [et al.]
  2. en.wikipedia.org
  3. Dos Santos L, et al. Serotonergic neurons in the median raphe nucleus regulate inhibitory avoidance but not escape behavior in the rat elevated T-maze test of anxiety.Psychopharmacology (Berl). 2005 Jun;179(4):733-41. Epub 2004 Dec 24.
  4. Gaspar P, et al. The developmental role of serotonin: news from mouse molecular genetics. Nature Reviews Neuroscience 4, 1002-1012 (December 2003) | doi:10.1038/nrn1256
  5. Gross C,et al. Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult.

Nature 416, 396-400 (28 March 2002) | doi:10.1038/416396a

  1. Severson C A et al. Midbrain serotonergic neurons are central pH chemoreceptors. Nature Neuroscience 6, 1139 - 1140 (2003)| doi:10.1038/nn1130

Additional information

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