The dorsal raphe nucleus is located on the midline of the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...

and is one of the raphe nuclei. It has rostral and caudal subdivisions. * The rostral aspect of the ''dorsal'' raphe is further divided into interfascicular, ventral, ventrolateral and dorsal subnuclei. * The projections of the ''dorsal'' raphe have been found to vary topographically, and thus the subnuclei differ in their projections. An increased number of cells in the lateral aspects of the dorsal raphe is characteristic of humans and other primates.

Serotonin

The dorsal raphe is the largest serotonergic nucleus and provides a substantial proportion of the serotonin innervation to the forebrain. Serotonergic neurons are found throughout the dorsal raphe nucleus and tend to be larger than other cells. A substantial population of cells synthesizing

substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its clos ...

are found in the rostral aspects, many of these co-express serotonin and substance P. There is also a population of catecholamine synthesizing neurons in the rostral dorsal raphe, and these cells appear to be relatively large. The dorsal raphe nucleus is rich in pre-synaptic serotonin 5-HT_1A

autoreceptors An autoreceptor is a type of Receptor (biochemistry), receptor located in the cell membrane, membranes of neuron, nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or ...

, and it's believed that the action of the

selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracell ...

(SSRIs) in this region is responsible for the latency of their antidepressant effect.

Projections

Ten percent of the axons from the nucleus raphe dorsalis of the rat have been shown to project to the

amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...

, while only medium cells seem to project to the caudate and putamen and olfactory bulb.

Role in naloxone-induced morphine withdrawal

The nucleus raphes dorsalis has also been implicated in naloxone-induced morphine withdrawal. It is known that endogenous

opioid receptors Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin r ...

exist on the nucleus raphes 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 raphes dorsalis can partially alleviate

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

withdrawal symptoms via electrical stimulation of the raphe nucleus in question. 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 raphes magnus and induced

analgesia Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...

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.

Role in narcolepsy

Wu M.F. ''et al.'' studied the nucleus raphes dorsalis as it pertained to

narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...

. This is logical, as the raphe nuclei have been known to play a role in the sleep/wake cycle.

Cataplexy Cataplexy is a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, or terror. Cataplexy affects approximately 70% of people who have narcolepsy, and is ...

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 Rem or REM may refer to: Music * R.E.M., an American rock band * ''R.E.M.'' (EP), by Green * "R.E.M." (song), by Ariana Grande Organizations * La République En Marche!, a French centrist political party * Reichserziehungsministerium, in Nazi G ...

sleep, when all muscle tone is lost except for the eyes. The nucleus raphes dorsalis have been known to project to the lateral

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

, along with the

locus coeruleus The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system. The locus coerule ...

and the

tuberomammillary nucleus The tuberomammillary nucleus (TMN) is a histaminergic nucleus located within the posterior third of the hypothalamus. It consists of, largely, histaminergic neurons (i.e., histamine-releasing neurons) and is involved with the control of arousal, l ...

. The neurotransmitters of these three aforementioned nuclei, which project to the lateral hypothalamus, are

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

and

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...

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 This glossary of medical terms is a list of definitions about medicine, its sub-disciplines, and related fields. A * Aarskog–Scott syndrome – (AAS) A rare, inherited (X-linked) disease characterized by short stature, facial abnormalities ...

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 Mephenesin (INN) is a centrally acting muscle relaxant. It can be used as an antidote for strychnine poisoning. Mephenesin however presents with the major drawbacks of having a short duration of action and a much greater effect on the spinal cord ...

, reduces activity of the dorsal nucleus, as well as microinjections of

carbachol Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. Thus it is classified as a cholinergic agonist. It is primarily used for var ...

(which induces atonia while awake).

Role in depression and suicide

The rostral raphe nuclei, both the

median raphe nucleus The median raphe nucleus (MRN or MnR), also known as the nucleus raphes medianus (NRM)Federative Committee on Anatomical Terminology (FCAT) (1998). ''Terminologia Anatomica''. Stuttgart: Thieme or superior central nucleus, is a brain region compos ...

and particularly the dorsal raphe nucleus have long been implicated in depression. Some studies have suggested that the dorsal raphe may be decreased in size in people with depression and, paradoxically, an increased cell density in those who die by suicide.

References

External links

NIF Search - Dorsal Raphe Nucleus
via the

Neuroscience Information Framework The Neuroscience Information Framework is a repository of global neuroscience web resources, including experimental, clinical, and translational neuroscience databases, knowledge bases, atlases, and genetic/ genomic resources and provides many aut ...

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