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|Brain: Raphe nuclei|
Section of the medulla oblongata at about the middle of the olive. (Raphe nuclei not labeled, but 'raphe' labeled at left.)
Horizontal cross section of the brainstem at the lower pons. The raphe nucleus is labeled #18 in the middle.
The raphe nuclei ("raffe", Greek: ῥαφή = seam ) 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. Selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to act in these nuclei, as well as at their targets.
In order from caudal to rostral, the raphe nuclei are known as the nucleus raphe obscurus, the nucleus raphe magnus, the nucleus raphe pontis, the nucleus raphe pallidus, the median raphe nucleus, dorsal raphe nucleus, nuclei linearis intermedius and linearis rostralis. Some scientists chose to group the nuclei lineares into one nucleus, shrinking the number of raphe to seven, e.g., NeuroNames makes the following ordering:
- Raphe nuclei of the midbrain reticular formation
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  instead of the grammatically incorrect nucleus raphe magnus. The spelling raphe/raphes however can also be contested as numerous sources 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. The edition of the Nomina Anatomica that was ratified in Jena in 1935 used rhaphe instead of raphe.
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 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 locate 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 disorder prognosis.
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.
Projections from the raphe nuclei also terminate in the dorsal horn of spinal gray matter where they regulate the release of enkephalins, which inhibit pain sensation.
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 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 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.
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