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The serotonin-producing neurons in the brainstem raphe nuclei have the largest and most complex efferent system in the human brain. It surpasses that described for the brainstem catecholamine-producing neurons or the descending cortical projecting system. The amino-acid transmitters are greater in absolute abundance throughout the brain, but they lack the strict anatomical boundaries characteristic of serotonin-producing neurons. In other words, the serotonergic neurons can exert a global influence, which is coordinated from a unified anatomical set of neurons. Glutamate, glycine, and GABA have neurons distributed throughout the brain, and these amino-acid transmitter neurons participate in local and projecting system that have no functional or anatomical cohesiveness. The special nature of the raphe brainstem neurons was recognized by the classical neuroanatomist Ramón y Cajal who described these giant neurons in the brainstem midline but was unable to follow their extensive projections. 

Dorsal Raphe Nucleus (DRN) The DRN is divided into medial, lateral (the wings), and caudal components. The medial component can be further divided into a mediodorsal (superior) and an interfascicular component. The superior component is in the central grey, just below the cerebral aqueduct. The interfascicular component surrounds the MLF and is especially prominent between the fasciculi.

Median Raphe Nucleus (MRN) The MRN is a paramedian and median cluster of cells lying below and caudal to the superior cerebellar decussation (SCD). Scattered 5-HT cells of the MRN are seen ventrolateral to the MLF. These laterally situated cells lie in the nucleus pontis centralis oralis and form a ring around the central tegmental tract, one of the most primitive ascending pathways carrying reticulothalamic axons. According to Olsewski and Baxter’s human brain atlas, the MRN is but one part of the larger superior central nucleus (SCN), which includes the interfascicular aspect of the DRN. Although there is substantial anatomical, developmental and functional evidence to support including the DRN interfascicular neurons in the SCN, current usage prescribes keeping the original classification of DRN and MRN proposed by Dahlstrom and Fuxe.

Nucleus Raphe Obscrus (NROb) This group (originally classified as B2) is a collection of large-medium multipolar neurons. They form a symmetrical paramedian cluster on either side of the midline. This dorsally situated nucleus extends from the caudal pons back into the cervical spinal cord. 5-HT neurons in the spinal cord lie ventral to the central canal and on the medial border of the ventral horn. The 5-HT neurons are commonly intermixed with the medial longitudinal fasciculus (MLF), the tectospinal tract (tst), and the dorsal aspect of the pyramidal decussation. The nucleus is more dense caudally in the medulla; at the level of cranial nerve VI, it is less densely packed than either the ventrally situated NRM or the NRPa. The extraraphe component of NRO was described in the human brain based on Nissl staining. These 5-HT neurons form a splinter group from NRO and lie just ventral to the fourth ventricle at the level of the VII cranial nucleus. These neurons were previously designated nucleus raphe ventricularis.

Nucleus Raphe Pallidus (NRpa) This group (originally designated as B1) is a group of medium sized multipolar 5-HT neurons in paramedian columns. The nucleus stretches from the cranial nerve XII to the anterior end of the inferior olive. The lateral aspects of the nucleus extend over the mediodorsal surface of the pyramidal tracts, while the main body of the nucleus lies between the pyramidal tracts. The cells appear to be contiguous with the NRM anteriorly and with the VLM laterally.

Nucleus Raphe Magnus (NRmg) This collection of medium to large 5-HT neurons extends from the rostral superior olive back to cranial nerve XII. This nucleus lies between NRPa and NRO, and at points the borders between these three nuclei are difficult to demarcate. The nucleus is invaded by both the trapezoid body and the dorsal border of the medial lemniscus. Occasionally, very large 5-HT neurons are seen more laterally in the boundary of the nucleus reticularis gigantocellularis.