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Journal of Chemical Neuroanatomy Dec 2003The raphe nuclei are distributed near the midline of the brainstem along its entire rostro-caudal extension. The serotonergic neurons are their main neuronal components,... (Review)
Review
The raphe nuclei are distributed near the midline of the brainstem along its entire rostro-caudal extension. The serotonergic neurons are their main neuronal components, although a proportion of them lie in subdivisions of the lateral reticular formation. They develop from mesopontine and medullary primordia, and the resulting grouping into rostral and caudal clusters is maintained into adulthood, and is reflected in the connectivity. Thus, the mesencephalon and rostral pons, neurons within the rostral raphe complex (caudal linear, dorsal raphe, and median raphe nuclei) project primarily to the forebrain. By contrast, in the caudal pons and medulla oblongata, neurons within the caudal raphe complex (raphe magnus, raphe obscurus, raphe pallidus nuclei and parts of the adjacent lateral reticular formation) project to the brainstem nuclei and to the spinal cord. The median raphe and dorsal raphe nuclei provide parallel and overlapping projections to many forebrain structures with axon fibers exhibiting distinct structural and functional characteristics. The caudal group of the serotonergic system projects to the brainstem, and, by three parallel projections, to the dorsal, intermediate and ventral columns in the spinal cord. The serotonergic axons arborize over large areas comprising functionally diverse targets. Some projections form classical chemical synapses while many do not, thus contributing to the so-called paracrine or volume transmission. The serotonergic projections participate in the regulation of different functional (motor, somatosensory, limbic) systems; and have been associated with a wide range of neuropsychiatric and neurological disorders. Finally, recent experimental data support the role of serotonin in modulating brain development, such that a dysfunction in serotonergic transmission during early life could lead to long lasting structural and functional alterations.
Topics: Animals; Brain Diseases; Humans; Neural Pathways; Neurons; Raphe Nuclei; Serotonin
PubMed: 14729135
DOI: 10.1016/j.jchemneu.2003.10.002 -
Okajimas Folia Anatomica Japonica 2012Along the raphe of the brain stem, a series of small neuronal groups can be observed in the medulla oblongata, the pons and the mesencephalon. The neurons located in and...
Along the raphe of the brain stem, a series of small neuronal groups can be observed in the medulla oblongata, the pons and the mesencephalon. The neurons located in and adjacent to the raphe are considered to produce mainly serotonin (5-HT). The groups of nuclei containing 5-HT were first reported in experimental animals in the early 1960s. The presence of such nuclei, however, has not yet been brought to light in the human brainstem except the few atlases, although in several neuroanatomy textbooks, extrapolated data are shown in the form of drawings as if they were the data from the human brain. The aim of this study is to present microscopic photos of such raphe nuclei made from serial sections of the human brainstem, and to clarify the differences between findings in human and textbook drawings from animal data.
Topics: Cerebellum; Female; Humans; Middle Aged; Raphe Nuclei
PubMed: 22975744
DOI: 10.2535/ofaj.89.15 -
Brain Research. Brain Research Reviews Sep 2002There is considerable interest in the regulation of the extracellular compartment of the transmitter serotonin (5-hydroxytryptamine, 5-HT) in the midbrain raphe nuclei... (Review)
Review
There is considerable interest in the regulation of the extracellular compartment of the transmitter serotonin (5-hydroxytryptamine, 5-HT) in the midbrain raphe nuclei because it can control the activity of ascending serotonergic systems and the release of 5-HT in terminal areas of the forebrain. Several intrinsic and extrinsic factors of 5-HT neurons that regulate 5-HT release in the dorsal (DR) and median (MnR) raphe nucleus are reviewed in this article. Despite its high concentration in the extracellular space of the raphe nuclei, the origin of this pool of the transmitter remains to be determined. Regardless of its origin, is has been shown that the release of 5-HT in the rostral raphe nuclei is partly dependent on impulse flow and Ca(2+) ions. The release in the DR and MnR is critically dependent on the activation of 5-HT autoreceptors in these nuclei. Yet, it appears that 5-HT autoreceptors do not tonically inhibit 5-HT release in the raphe nuclei but rather play a role as sensors that respond to an excess of the endogenous transmitter. Both DR and MnR are equally responsive to the reduction of 5-HT release elicited by the local perfusion of 5-HT(1A) receptor agonists. In contrast, the effects of selective 5-HT(1B) receptor agonists are more pronounced in the MnR than in the DR. However, the cellular localization of 5-HT(1B) receptors in the raphe nuclei remains to be established. Furthermore, endogenous noradrenaline and GABA tonically regulate the extracellular concentration of 5-HT although the degree of tonicity appears to depend upon the sleep/wake cycle and the behavioral state of the animal. Glutamate exerts a phasic facilitatory control over the release of 5-HT in the raphe nuclei through ionotropic glutamate receptors. Overall, it appears that the extracellular concentration of 5-HT in the DR and the MnR is tightly controlled by intrinsic serotonergic mechanisms as well as afferent connections.
Topics: Afferent Pathways; Animals; Behavior; Carrier Proteins; Extracellular Space; Humans; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Raphe Nuclei; Receptors, Serotonin; Serotonin; Serotonin Plasma Membrane Transport Proteins; Sleep; Stress, Psychological
PubMed: 12423765
DOI: 10.1016/s0165-0173(02)00182-0 -
The Journal of Comparative Neurology Jul 1995The vertebrate reticular formation, containing over 30 nuclei in mammals, is a core brainstem area with a long evolutionary history. However, not all reticular nuclei...
The vertebrate reticular formation, containing over 30 nuclei in mammals, is a core brainstem area with a long evolutionary history. However, not all reticular nuclei are equally old. Nuclei that are widespread among the vertebrate classes are probably ones that evolved early. We describe raphe nuclei in the reticular formation of three cartilaginous fishes that diverged from a common ancestor over 350 million years ago. These fishes are Hydrolagus colliei, a holocephalan, Squalus acanthias, a small-brained shark, and Heterodontus francisci, a large-brained shark. Nuclear identification was based on immunohistochemical localization of serotonin and leu-enkephalin, on brainstem location, and on cytoarchitectonics. Raphe nuclei are clustered in inferior and superior cell groups, but within these groups individual nuclei can be identified: raphe pallidus, raphe obscurus, and raphe magnus in the inferior group and raphe pontis, raphe dorsalis, raphe centralis superior, and raphe linearis in the superior group. Hydrolagus lacked a dorsal raphe nucleus, but the nucleus was present in the sharks. The majority of immunoreactive cells are found in the superior group, especially in raphe centralis superior, but immunoreactive cells are present from spinal cord to caudal mesencephalon. The distribution and cytoarchitectonics of serotoninergic and enkephalinergic cells are similar to each other, but raphe nuclei contain fewer enkephalinergic than serotoninergic cells. The cytoarchitectonics of immunoreactive raphe cells in cartilaginous fishes are remarkably similar to those described for raphe nuclei in mammals; however, the lack of a raphe dorsalis in Hydrolagus indicates that either it evolved later than the other raphe nuclei or it was lost in holocephalan fishes.
Topics: Animals; Biological Evolution; Dogfish; Elasmobranchii; Enkephalin, Leucine; Immunohistochemistry; Raphe Nuclei; Serotonin; Sharks
PubMed: 7560295
DOI: 10.1002/cne.903580308 -
American Journal of Physiology.... Jun 2023The supraspinal brain regions controlling defecation reflex remain to be elucidated. The purpose of this study was to determine the roles of the hypothalamic A11 region...
The supraspinal brain regions controlling defecation reflex remain to be elucidated. The purpose of this study was to determine the roles of the hypothalamic A11 region and the medullary raphe nuclei in regulation of defecation. For chemogenetic manipulation of specific neurons, we used the double virus vector infection method in rats. hM3Dq or hM4Di was expressed in neurons of the A11 region and/or the raphe nuclei that send output to the lumbosacral defecation center. Immunohistological and functional experiments revealed that both the A11 region and the raphe nuclei directly connected with the lumbosacral spinal cord through descending pathways composed of stimulatory monoaminergic neurons. Stimulation of the hM3Dq-expressing neurons in the A11 region or the raphe nuclei enhanced colorectal motility only when GABAergic transmission in the lumbosacral spinal cord was blocked by bicuculline. Experiments using inhibitory hM4Di-expressing rats revealed that enhancement of colorectal motility caused by noxious stimuli in the colon is mediated by both the A11 region and the raphe nuclei. Furthermore, suppression of the A11 region and/or the raphe nuclei significantly inhibited water avoidance stress-induced defecation. These findings demonstrate that the A11 region and the raphe nuclei play an essential role in the regulation of colorectal motility. This is important because brain regions that mediate both intracolonic noxious stimuli-induced defecation and stress-induced defecation have been clarified for the first time. The A11 region and the raphe nuclei, constituting descending pain inhibitory pathways, are related to both intracolonic noxious stimuli-induced colorectal motility and stress-induced defecation. Our findings may provide an explanation for the concurrent appearance of abdominal pain and defecation disorders in patients with irritable bowel syndrome. Furthermore, overlap of the pathway controlling colorectal motility with the pathway mediating stress responses may explain why stress exacerbates bowel symptoms.
Topics: Animals; Rats; Colorectal Neoplasms; Medulla Oblongata; Raphe Nuclei; Spinal Cord
PubMed: 37096901
DOI: 10.1152/ajpgi.00019.2023 -
Neuroscience Research Jun 2019The ventral respiratory column (VRC) generates rhythmical respiration and is divided into four compartments: the Bötzinger complex (BC), pre-Bötzinger complex (PBC),...
The ventral respiratory column (VRC) generates rhythmical respiration and is divided into four compartments: the Bötzinger complex (BC), pre-Bötzinger complex (PBC), rostral ventral respiratory group (rVRG), and caudal ventral respiratory group (cVRG). Serotonergic nerve fibers are densely distributed in the rostral to caudal VRC and serotonin would be one of the important modulators for the respiratory control in the VRC. In the present study, to elucidate detailed distribution of serotonergic neurons in raphe nuclei projecting to the various rostrocaudal levels of VRC, we performed combination of retrograde tracing technique by cholera toxin B subunit (CTB) with immunohistochemistry for tryptophan hydroxylase 2 (TPH2). The double-immunoreactive neurons with CTB and TPH2 were distributed in the both rostral and caudal raphe nuclei, i.e. dorsal raphe nucleus, raphe magnus nucleus, gigantocellular reticular nucleus alpha and ventral parts, lateral paragigantocellular nucleus, parapyramidal area, raphe obscurus nucleus, and raphe pallidus nucleus. The distributions of double-immunoreactive neurons were similar among injection groups of BC, PBC, anterior rVRG, and posterior rVRG/cVRG. In conclusion, serotonergic neurons in both rostral and caudal raphe nuclei projected throughout the VRC and these serotonergic projections may contribute to respiratory responses to various environmental and vital changes.
Topics: Animals; Cholera Toxin; Male; Medulla Oblongata; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Raphe Nuclei; Rats; Rats, Wistar; Respiratory Center; Serotonergic Neurons; Serotonin; Tryptophan Hydroxylase
PubMed: 29803764
DOI: 10.1016/j.neures.2018.05.004 -
The Journal of Comparative Neurology Sep 1979The raphe nuclei of the rabbit brain stem were found in the midline and adjacent reticular formation of the medulla, pons, and mesencephalon. Nuclei raphe obscurus,...
The raphe nuclei of the rabbit brain stem were found in the midline and adjacent reticular formation of the medulla, pons, and mesencephalon. Nuclei raphe obscurus, pallidus, and magnus were located in the medulla. Nucleus raphe pontis and the caudal portion of nuclei raphe dorsalis and centralis superior were present in the pons. The rostral portion of nuclei raphe dorsalis and centralis superior, and nuclei linearis caudalis and intermedius were present in the msencephalon. Wings of neurons extended from the midline clusters of raphe neurons into the adjacent reticular formation. These wings of neurons contained serotonergic perikarya which were cytoarchitecturally indistinguishable from the midline neurons. A detailed localization of these nuclei is presented in atlas form. These raphe nuclei contained heterogeneous populations of neurons which varied in the size, shape and density of the cell bodies. In addition, the dendritic branching, specific orientation of dendrites, and appearance of spines were distinct for each of the raphe nuclei. Individual raphe nuclei often contained several subpopulations of neurons characterized by unique spatial configuration and orientation. The main morphological similarities of the raphe nuclei are location in or adjacent to the midline, the presence of serotonergic cell bodies in all raphe nuclei except the linear nuclei, and heterogeneous cell populations.
Topics: Afferent Pathways; Animals; Brain Mapping; Brain Stem; Cats; Efferent Pathways; Haplorhini; Medulla Oblongata; Mesencephalon; Pons; Rabbits; Raphe Nuclei; Rats; Saimiri; Species Specificity
PubMed: 114552
DOI: 10.1002/cne.901870112 -
NeuroImage Jan 2012The brainstem contains various important monoaminergic neuronal centers, including the raphe nuclei which contain serotonergic neurons. The raphe nuclei, however, are...
UNLABELLED
The brainstem contains various important monoaminergic neuronal centers, including the raphe nuclei which contain serotonergic neurons. The raphe nuclei, however, are not easily identifiable and located by conventional neuroimaging.
METHODS
Fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) were performed in seven healthy subjects using a new PET-MRI, which consists of a high-resolution research tomograph (HRRT) PET and 7.0 T-MRI. Glucose metabolism of raphe nuclei was semiquantitatively measured and identified along the midline brainstem region in vivo.
RESULTS
Midline nuclei clustered in four groups appeared to be the raphe nuclei and could be clearly visualized; specifically, we identified the groups as the dorsal raphe, raphe reticularis centralis superior, raphe pontis, and raphe magnus group.
CONCLUSION
FDG imaging of the midline raphe nuclei in vivo could potentially be an important tool for investigating brain diseases as well as conducting functional brain studies in the context of sleep disorders, depression, and neurodegenerative disease.
Topics: Female; Fluorodeoxyglucose F18; Glucose; Humans; Magnetic Resonance Imaging; Male; Metabolic Clearance Rate; Positron-Emission Tomography; Radiopharmaceuticals; Raphe Nuclei; Subtraction Technique; Tissue Distribution; Young Adult
PubMed: 21963920
DOI: 10.1016/j.neuroimage.2011.09.036 -
Progress in Brain Research 2014The medullary raphé nuclei participate in the regulation of breathing and airway defensive reflexes. Our focus was to analyze the effects of codeine and kainic acid...
The medullary raphé nuclei participate in the regulation of breathing and airway defensive reflexes. Our focus was to analyze the effects of codeine and kainic acid within the medullary raphé on coughing, sneezing, solitary expulsions, and concomitant breathing changes using models of anesthetized cats (n=12) and rabbits (n=15) and microinjection techniques. Our findings are consistent with (1) involvement of neurons within the medullary raphé in the generation of the cough motor pattern by a codeine-sensitive and -insensitive mechanisms, (2) a contribution of raphé nuclei to the control of expiratory efforts, (3) limited contribution of the medullary raphé to the cough-gating mechanism, (4) minor contribution of respiration/coughing neuronal network, including the portion within raphé nuclei and the respiratory/cough central pattern generator, to the production of the sneeze reflex motor pattern.
Topics: Animals; Cats; Central Pattern Generators; Cough; Rabbits; Raphe Nuclei; Respiratory Physiological Phenomena
PubMed: 25194203
DOI: 10.1016/B978-0-444-63488-7.00014-8 -
The European Journal of Neuroscience May 2020Neuronal nitric oxide synthase (nNOS) catalyses the production of the neurotransmitter nitric oxide. nNOS is expressed in the dorsal raphe nucleus (DRN), a source of...
Neuronal nitric oxide synthase (nNOS) catalyses the production of the neurotransmitter nitric oxide. nNOS is expressed in the dorsal raphe nucleus (DRN), a source of ascending serotonergic projections. In this study, we examined the distribution nNOS and the function of nitric oxide in the DRN and adjacent median raphe nucleus (MRN) of the rat. We hypothesized that nNOS is differentially expressed across the raphe nuclei and that nitric oxide influences the firing activity of a subgroup of 5-HT neurons. Immunohistochemistry revealed that, nNOS is present in around 40% of 5-HT neurons, throughout the DRN and MRN, as well as in some non-5-HT neurons immediately adjacent to the DRN and MRN. The nitric oxide receptor, soluble guanylyl cyclase, was present in all 5-HT neurons examined in the DRN and MRN. In vitro extracellular electrophysiology revealed that application of the nitric oxide donor, diethylamine NONOate (30-300 µM) inhibited 60%-70% of putative 5-HT neurons, excited approximately 10% of putative 5-HT neurons and had no effect on the rest. The inhibitory response to nitric oxide was blocked by [1H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one (ODQ, 30 or 100 µM), indicating mediation by soluble guanylyl cyclase. Juxtacellular labelling revealed that nitric oxide inhibits firing in both putative 5-HT neurons which express nNOS and those which do not express nNOS. Our data are consistent with the notion that nitric oxide acts as both a trans-synaptic and autocrine signaller in 5-HT neurons in the DRN and MRN and that its effects are widespread and primarily inhibitory.
Topics: Animals; Dorsal Raphe Nucleus; Midbrain Raphe Nuclei; Neurons; Nitric Oxide; Rats; Serotonin
PubMed: 32115781
DOI: 10.1111/ejn.14713