Raphe nuclei

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 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.

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, 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.

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 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 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.

Sleep and arousal regulation

According to Michel Jouve from Lyon, there is a contradiction in study findings regarding the relationship between serotonin and sleep: initially, serotonin was believed to act as a neuromodulator of sleep, as destruction of serotonergic neurons in the raphe nuclei or inhibition of serotonin synthesis induced severe insomnia. However, studies showed that the electrical activity of serotonergic cell bodies and serotonin release increases during wakefulness and decreases during sleep, which appears at first glance to contradict the idea of serotonin contributing to sleep. For the same author, serotonin release during wakefulness can trigger a cascade of genomic events in some sleep-promoting neurons in the preoptic area, allowing it under certain conditions to also contribute to increased sleep propensity and regulation of slow-wave sleep, Cespigluou, from the same laboratory, explains that serotonin (5-HT) participates in sleep in two distinct ways. First, when released during wakefulness via axonal nerve endings, it influences the synthesis of sleep-promoting substances in specific brain regions. Second, when released during sleep within the dorsal raphe nucleus by dendrites of serotonergic neurons, it contributes to silencing serotonergic cell bodies through an auto-inhibitory process.

According to Monti from Uruguay, who based his conclusions on electrophysiological, neurochemical, genetic, and neuropharmacological approaches, serotonin (5-HT) originating from the dorsal raphe nucleus primarily promotes wakefulness and inhibits rapid eye movement (REM) sleep, the stage during which dreaming occurs. For Barbara Estone Jones, Serotonergic raphe neurons promote a seemingly quiet or satiated waking state, which though exclusive of REMS, can actually be conducive to SWS

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 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.