The raphe nuclei (, "seam") are a moderate-size cluster of nuclei found in the

brain stem 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 co ...

. They have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. They function as

autoreceptor 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 ...

s in the brain and decrease the release of

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

. The

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

drug

Buspirone Buspirone, sold under the brand name Buspar among others, is an anxiolytic, a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder (GAD). It is a serotonin 5-HT1A receptor, 5-HT1A receptor partial ag ...

acts as

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

against these receptors.

Selective serotonin reuptake inhibitor 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 primarily work by blo ...

(SSRI)

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s are believed to act in these nuclei, as well as at their targets.

Anatomy

The raphe nuclei are traditionally considered to be the medial portion of the

reticular formation The reticular formation is a set of interconnected nuclei in the brainstem that spans from the lower end of the medulla oblongata to the upper end of the midbrain. The neurons of the reticular formation make up a complex set of neural networks ...

, and appear as a ridge of cells in the center and most medial portion of the

. In order from caudal to

rostral Rostral may refer to: Anatomy * Rostral (anatomical term), situated toward the oral or nasal region * Rostral bone, in ceratopsian dinosaurs * Rostral organ, of certain fish * Rostral scale The rostral scale, or rostral, in snakes and other sca ...

, the raphe nuclei are known as the '' nucleus raphe obscurus'', the '' nucleus raphe pallidus'', the ''

nucleus raphe magnus The nucleus raphe magnus (NRM) is one of the seven raphe nuclei. It is situated in the pons in the brainstem, just rostral to the nucleus raphe obscurus. The NRM receives afferent stimuli from the enkephalinergic neurons of the periaqueductal ...

'', the '' nucleus raphe pontis'', the '' median raphe nucleus'', ''

dorsal raphe nucleus The dorsal raphe nucleus is one of the raphe nuclei. It is situated in the brainstem at the midline. It has rostral and caudal subdivisions: * The rostral aspect of the ''dorsal'' raphe is further divided into interfascicular, ventral, ventrolater ...

'', ''caudal linear nucleus''. In the first systematic examination of the raphe nuclei, Taber ''et al.''. (1960) originally proposed the existence of two linear nuclei (nucleus linearis intermedius and nucleus linearis rostralis). This study was published before techniques enabling the visualization of serotonin or the enzymes participating in its synthesis had been developed, as first demonstrated by Dahlström and Fuxe in 1964. Later, it was revealed that of these two nuclei, only the former (nucleus linearis intermedius, now known as the caudal linear nucleus), proved to contain serotonin-producing neurons, though both of them contain dopaminergic neurons. In some works (e.g.), researchers have grouped the nuclei lineares into one nucleus, the ''nucleus linearis'', shrinking the number of raphe to seven, e.g., NeuroNames makes the following ordering: * Raphe nuclei of

medulla oblongata The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (involun ...

** Nucleus raphe obscurus **

Nucleus raphe magnus The nucleus raphe magnus (NRM) is one of the seven raphe nuclei. It is situated in the pons in the brainstem, just rostral to the nucleus raphe obscurus. The NRM receives afferent stimuli from the enkephalinergic neurons of the periaqueductal ...

** Nucleus raphe pallidus * Raphe nuclei of the pontine reticular formation ** Nucleus raphe pontis ** Nucleus centralis inferior * Raphe nuclei of the

midbrain The midbrain or mesencephalon is the uppermost portion of the brainstem connecting the diencephalon and cerebrum with the pons. It consists of the cerebral peduncles, tegmentum, and tectum. It is functionally associated with vision, hearing, mo ...

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 In grammar, the genitive case ( abbreviated ) is the grammatical case that marks a word, usually a noun, as modifying another word, also usually a noun—thus indicating an attributive relationship of one noun to the other noun. A genitive ca ...

''raphes'' ('of the seam') instead of the

nominative case In grammar, the nominative case ( abbreviated ), subjective case, straight case, or upright case is one of the grammatical cases of a noun or other part of speech, which generally marks the subject of a verb, or (in Latin and formal variants ...

''raphe'' ('seam') in these Latin expressions. The main authority in anatomical names,

Terminologia Anatomica ''Terminologia Anatomica'' (commonly abbreviated TA) is the international standard for human anatomy, human anatomical terminology. It is developed by the Federative International Programme on Anatomical Terminology (FIPAT) a program of the Inter ...

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 sourcesHyrtl, J. (1880). ''Onomatologia Anatomica. Geschichte und Kritik der anatomischen Sprache der Gegenwart.'' Wien: Wilhelm Braumüller. K.K. Hof- und Universitätsbuchhändler. indicate that ''raphe'' is an incorrect Latin rendering of the Ancient Greek word ῥαφή as the initial letter rho with

rough breathing In the polytonic orthography of Ancient Greek, the rough breathing ( or ; ) character is a diacritical mark used to indicate the presence of an sound before a vowel, diphthong, or after rho. It remained in the polytonic orthography even af ...

(''spiritus asper'') is normally rendered as ''rh'' in Latin. The edition of the

Nomina Anatomica ''Nomina Anatomica'' (''NA'') was the international standard on human anatomic terminology from 1895 until it was replaced by '' Terminologia Anatomica'' in 1998. In the late nineteenth century some 30,000 terms for various body parts were in us ...

that was ratified in

Jena Jena (; ) is a List of cities and towns in Germany, city in Germany and the second largest city in Thuringia. Together with the nearby cities of Erfurt and Weimar, it forms the central metropolitan area of Thuringia with approximately 500,000 in ...

in 1935 used ''rhaphe'' instead of ''raphe''.

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 called median raphe nucleus, mRN) and nucleus raphe dorsalis (dRN) project towards the brain areas of higher function The numerous projections from the mRN and dRN to key brain structures make serotonergic system fundamental in regulating brain homeostasis. However, studies also show feedback loops from numerous areas of the brain controlling the serotonergic neurons located in the nucleus raphe dorsalis, including the orbital cortex,

cingulate cortex The cingulate cortex is a part of the brain situated in the medial aspect of the cerebral cortex. The cingulate cortex includes the entire cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the cin ...

, medial preoptic area, lateral preoptic area, and several areas of the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

. 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 Obsession may refer to: Psychology * Celebrity worship syndrome, obsessive addictive disorder to a celebrity's personal and professional life * Obsession (psychology), a persistent attachment to an object or idea * Fixation (psychology), persi ...

prognosis. Dopamine_and_serotonin_pathways

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

, 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 hypothalamic 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.

Thermoregulation

A large increase in sympathetic nerve activity was observed when an excitatory amino acid was injected into the raphe pallidus, resulting in both brown adipose tissue (BAT) temperature and heart rate increasing. This suggests that activation of the raphe nucleus results in an increase in sympathetic activity to the BAT. The raphe pallidus wasn't switched off using 8-OH-DPAT, which in turn reduced body temperature due to a reduced response to cold. This suggests the importance of the raphe nucleus in responding appropriately to the cold.

The raphe nuclei and the effects of ghrelin

More recent studies of the Raphe Nuclei done with rats involve the effects of

ghrelin Ghrelin (; or lenomorelin, INN) is a hormone primarily produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrel ...

on the

. When administered, larger doses of ghrelin act centrally on the raphe nucleus,

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

, and

amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...

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 structure of the nucleus. Changes also occur after 24 hours suggesting delayed modifications as well.

Anatomy

Nomenclature

Projections

Function

Thermoregulation

The raphe nuclei and the effects of ghrelin

See also

References

Further reading