The DMV, along with the Nucleus Ambiguous (NA) and raphe obscurus (RO) regulates a variety of autonomic reflexes, suggesting that there may be an association between the degree of neurodegenerative protein aggregation in the DMV and symptomatic autonomic dysfunction in patients with LBD. 
Compared with the control, the MSA group showed a marked depletion of neurons in the IML (38.0 +/- 7.1 versus 75.2 +/- 7.6 cells, P < 0.001), thyrosine hydroxylase-immunoreactive neurons in the ventrolateral medulla (VLM) (17.4 +/- 5.1 versus 72.8 +/- 13.6 cells, P < 0.01) and tryptophan hydroxylase-immunoreactive neurons in the VLM (15.6 +/- 9.2 versus 60.8 +/- 17.0 cells, P < 0.01), nucleus raphe obscurus (19.3 +/- 4.4 versus 75.3 +/- 8.6 cells, P < 0.001), nucleus raphe pallidus (2.1 +/- 2.7 versus 9.0 +/- 3.4 cells, P < 0.03), and arcuate nucleus (0.4 +/- 0.8 versus 2.3 +/- 1.5 cells, P < 0.05). Moreover, in patients who succumbed to sudden death, when compared with patients who had established causes of death, we found a marked depletion of tryptophan hydroxylase-immunoreactive neurons in the VLM (7.3 +/- 3.5 versus 21.8 +/- 6.5 cells, P < 0.02) and nucleus raphe obscurus (15.0 +/- 2.0 versus 22.5 +/- 2.1 cells, P < 0.01).
RESULTS: Values of binding potential for hippocampus (1.2), entorhinal cortex (1.1), septum (1.1), medial prefrontal cortex (1.0), amygdala (0.8), raphe nuclei (0.6), paraventricular hypothalamic nucleus (0.5) and raphe obscurus (0.5) were comparable to those previously measured with PET in cats, non-human primates or humans.
The midline medulla oblongata, which includes the nucleus raphe obscurus, raphe magnus and raphe pallidus (NRP), is involved in regulation of cardiovascular responses.
Simultaneous inhibition of the retrotrapezoid nucleus (RTN) and raphe obscurus (ROb) decreased the systemic CO(2) response by 51%, an effect greater than inhibition of RTN (-24%) or ROb (0%) alone, suggesting that ROb modulates chemoreception by interaction with the RTN (19).
Immunoreactivities for Kir1.1 and Kir2.3 were observed in the nerve cell bodies and glial cells both in the chemosensory areas [ nucleus tractus solitarius (NTS), nucleus raphe obscurus (RO), pre-Bötzinger complex (PreBötC)] and non-chemosensory area [ hypoglossal nucleus (XII), inferior olive nucleus (IO)].
However, in the presence of FFA, local microinjection of 10 microM RIL in the raphe obscurus causes rhythm cessation, which suggests that I(NaP) regulates the excitability of neurons outside the preBötC, including serotonergic raphe neurons that project to, and help maintain, rhythmic preBötC function..
Just over half of them are found at the pontomedullary junction within raphe obscurus, raphe magnus, and gigantocellular nucleus pars alpha.
Moreover, anatomic evidence suggests that nucleus raphe obscurus (ROb) is a source of 5-HT-containing terminals within the NTS.
We observed that an intravenous (i.v.) injection of (+)-bicuculline, a GABA(A) receptor antagonist, significantly reduced respiratory inhibition induced by electrical stimulation of the raphe magnus (RM) or the raphe obscurus (RO).
The following results were obtained: (1) At PND 3, numerous CTb-labeled neurons (CTLN) were already present in the raphe pallidus (B1), while few CTLN were seen in raphe obscurus (B2) and raphe magnus (B3).
Neurons in the dorsal vagal complex including the dorsal motor nucleus of the vagus (DMN) express thyrotropin-releasing hormone (TRH) receptor and are innervated by TRH fibers originating from TRH synthesizing neurons in the raphe pallidus, raphe obscurus and the parapyramidal regions.
Microdialysis probes were also implanted into the nucleus raphe obscurus (NRO).
The brainstem had markedly stained fibers in the medial longitudinal fasciculus and localized neuronal cell body labeling in the red n, mesencephalic trigeminal n, lateral reticular n, raphe obscurus n, solitary n, compact ambiguus n, motor trigeminal n and n of trapezoid body.
raphe obscurus (NRO) and pallidus (NRP)] or the mesencephalon [ n.
Raphe pallidus and raphe obscurus did not show any differences among experimental groups.
Train pulse stimuli (100 Hz, 10-30 microA) were applied in the regions of the caudal raphe nuclei: the raphe magnus (RM), raphe pallidus (RP) and raphe obscurus (RO).
Single-unit activity of serotonergic neurons in the nuclei raphe obscurus (NRO) and raphe pallidus (NRP) were recorded in conjunction with heart rate in freely moving cats in response to systemic administration of vasoactive drugs and to graded haemorrhage.
These movements ultimately formed elements of several nuclei, aligned in four longitudinal bands: dorsal (including the gracile, cuneate, cochlear, and vestibular nuclei, plus cerebellar granular cells), dorsal intermediate (including trigeminal sensory, parvicellular reticular, and deep cerebellar nuclei), ventral intermediate (including lateral and intermediate reticular nuclei), and ventral (including the raphe obscurus and pontine nuclei).
Efferent projections towards the raphe obscurus from both medial and lateral caudal parapyramidal regions were found.
In addition, a large number of Fos-labelled cells were seen after PS rebound in the lateral, ventrolateral and dorsal periaqueductal grey, dorsal and lateral paragigantocellular reticular nuclei and the nucleus raphe obscurus.
All three components of the caudal raphe nuclei, raphe pallidus, raphe obscurus, and parapyramidal nucleus, are innervated by orexin-A-immunoreactive fibers.
Cell numbers were reduced in both the raphe obscurus and raphe pallidus.
Muscle tone inhibition was consistently found on or near the midline within the ventromedial medulla, dorsal to the inferior olive, in an area that includes the nucleus gigantocellularis, nucleus paramedianus, and raphe obscurus.
Serotonergic neurons not activated by hemorrhage were located in the nucleus raphe pallidus, the parapyramidal cell group, the raphe obscurus (RO), and the B3 region.
The highest density of immunoreactive fibers containing methionine-enkephalin-Arg(6)-Gly(7)-Leu(8) was found in the spinal trigeminal nucleus, the central gray and the reticular formation of the medulla oblongata, pons and mesencephalon, the solitary nucleus, the spinal vestibular nucleus, the dorsal accessory olivary nucleus, the raphe obscurus, the substantia nigra and in the interpeduncular nucleus.
There was a severe depletion of serotonergic neurons in the nucleus raphe magnus, raphe obscurus, raphe pallidus, and ventrolateral medulla in MSA.
In the present study, 2DG-induced Fos expression was examined in the solitary tract nucleus (NTS), hypothalamic paraventricular nucleus (PVN), raphe obscurus nucleus (ROb) and raphe pallidus nucleus (RPa), which have been previously suggested to be involved in glucoprivation-induced suppression of LH secretion in female rats.
The present study investigated in vitro changes in intracellular calcium concentrations ([ Ca(2+)](i)) in response to low (2 mm) or high (20 mm) extracellular glucose concentrations in isolated cells from the wall of the central canal (CC), raphe obscurus nucleus (ROb), ventromedial hypothalamus (VMH), and lateral hypothalamic area (LHA) in male rats.
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.
However, the number and proportion of the 5-HT/Fos co-localized neurons in the median raphe nucleus and nucleus raphe obscurus of the rat subjected to visceral noxious stimulation were statistically greater than those in rats subjected to somatic noxious stimulation. These results suggest that serotonergic neurons in median raphe nucleus and nucleus raphe obscurus have a tendency to higher neuronal activity after visceral noxious stimulation..
Our aim was to determine the effects of focal acidification in the raphe obscurus (RO) and raphe pallidus (RP) on ventilation and other physiological variables in both the awake and sleep states in adult goats.
ambiguus, rostroventrolateral n., C3 adrenaline cell group, raphe obscurus n., raphe pallidus n., raphe magnus n., lateral paragigantocellular reticular n., locus coeruleus, subcoeruleus n., Kolliker-Fuse n., A5 cell group, central gray matter, paraventricular hypothalamic n.
In the caudal ventrolateral medulla and raphe obscurus, 96% and 89%, respectively, of neuronal NO synthase containing neurones also express P2X(2) receptor subunit.
To determine whether changes were limited to the PBC, the present study aimed at examining the expression of CO in a number of brain stem nuclei, with or without known respiratory functions from P0 to P21 in rats: the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, nucleus raphe obscurus, dorsal motor nucleus of the vagus nerve, medial accessory olivary nucleus, spinal nucleus of the trigeminal nerve, and medial vestibular nucleus (MVe).
After unilateral iontophoretic injections of Fluoro-Gold into the vestibular nuclei, retrogradely labeled neurons were found in the dorsal raphe nucleus (including the dorsomedial, ventromedial and lateral subdivisions) and nucleus raphe obscurus, and to a minor extent in nucleus raphe pallidus and nucleus raphe magnus. Thus, the dorsal raphe nucleus sends projections that terminate predominantly in the rostral and medial aspects of the vestibular nuclear complex, while nucleus raphe obscurus projects relatively uniformly throughout the vestibular nuclei.
Discrete injection of the tracer Cholera toxin, subunit B, (ChB) was centred in the rat SCN, and a few retrograde labelled neurones were distributed in the dorsal and median raphe nuclei (MnR) and in the rostral part of the raphe magnus (RMg), but no neurones were found in the raphe pallidus or raphe obscurus.
The aim of the present study is to investigate if the nucleus raphe obscurus (NRO) participate in regulating the gallbladder motility in rabbits.
The largest number of such neurons was located in the rostral ventromedial medulla within the ventral gigantocellular nucleus, gigantocellular nucleus pars alpha, raphe obscurus, and raphe magnus.
Noxious cutaneous mechanical stimulation significantly increased the proportions of neurons double-labelled for Fos and GABA(B) receptors in several brainstem regions, namely, the reticular formation of the caudal ventrolateral medulla (VLMlat and VLMrf), lateral reticular nucleus, spinal trigeminal nucleus, pars caudalis (Sp5C), nucleus of the solitary tract, dorsal reticular nucleus, ventral reticular nucleus, raphe obscurus nucleus and dorsal parabrachial nucleus (DPB).
RESULTS: Chronic ethanol treatment, as delivered in the present experiment, induced a significant increase in the rate of 5-HT synthesis in descending serotonergic cell bodies (raphe pallidum, raphe obscurus, raphe magnus), nigrostriatal structures, the hippocampus and cortices.
Moreover, immunoreactive cell bodies were found in the inferior colliculus, the raphe obscurus, the nucleus prepositus hypoglossi, and in the midline of the anterior medulla oblongata.
raphe obscurus and pallidus), or motor activity (n. raphe obscurus and pallidus).
The aim of the present study was to investigate the role of nucleus raphe obscurus (NRO) in regulating the motility of sphincter of Oddi (SO).
To evaluate the involvement of serotonergic raphe nuclei, we compared the percentage of neurons synthesizing serotonin in the nucleus centralis superior (NCS), raphe obscurus and pallidus (NROP) in Alzheimer's disease (AD), progressive supranuclear palsy (PSP), Parkinson's disease (PD), multiple system atrophy (MSA), and control brains.
A parallel Fos detection tends to indicate that the changes of the respiratory rhythm may be due to a decrease in neuronal activity of medullary structures such as the ventrolateral subdivision of the solitary tract, the area postrema, and the nucleus raphe obscurus. In addition, the hypoxic respiratory depression is clearly emphasized after in utero exposure to caffeine and coincides with an increased Fos expression in the area postrema and nucleus raphe obscurus, two structures in which it is not increased in the absence of caffeine.
Both serotonergic and nonserotonergic pathways from the dorsal raphe nucleus and the nucleus raphe obscurus also project differentially to the vestibular nuclei, and 5-HT(2A) receptors are expressed in amygdaloid and cortical targets of the PBN.
The caudal cluster consisted of three divisions: the raphe obscurus nucleus, the raphe pallidus nucleus and the raphe magnus nucleus. The raphe obscurus nucleus was associated with the dorsal midline at the caudal-most part of the medulla oblongata. Raphe magnus was associated with the midline of the medulla and was found rostral to both the raphe obscurus and raphe pallidus.
These results are in contrast with our observations of the discrete projections of the caudal nucleus raphe obscurus, which target the autonomic and somatic MNs involved specifically in sexual and eliminative functions (Hermann et al.
Pressor responses elicited by stimulation of the nucleus raphe obscurus (NRO) depend on the integrity of the rostral ventrolateral medulla (RVLM).
Serotonergic single-unit activity during glucoregulatory challenges was studied in the nuclei raphe obscurus (NRO) and raphe pallidus (NRP) of freely moving cats.
A total of 23 neurons with decrementing firing patterns during the I phase were recorded in the raphe obscurus and pallidus at the levels of 2.0-4.0 mm rostral to the obex.
Previous research using microinjections of excitatory amino acids suggested that the caudal midline medulla (including nucleus raphe obscurus and nucleus raphe pallidus) contained a mixed population of sympathoexcitatory and sympathoinhibitory neurones.
Major sources of serotonergic input to the RVLM were shown to include the raphe obscurus, raphe pallidus and raphe magnus with a minor contribution from the ventrolateral, lateral and ventral regions of the periaqueductal gray matter, and the dorsal raphe nucleus.
Rat preparations were used to investigate long-term changes in external anal sphincter (EAS) contractions and reflexive penile erection following electrolytic lesions of the nucleus raphe obscurus (nRO) or the rostral ventrolateral medulla.
The gastric secretagogue response to stimulation of the raphe obscurus (mediated by TRH release into the dorsal vagal complex) was inhibited 50% by pretreatment with intracisternal dorsal medullary methiothepin (0.1 nmol/10 microl).
A few double-labeled neurons were also observed in nucleus raphe obscurus and nucleus raphe magnus.
At this survival time several brain stem nuclei including the A5 noradrenergic cell group, the caudal raphe nuclei (raphe obscurus, raphe pallidus, raphe magnus), the A1/C1 noradrenergic and adrenergic cell group, the nucleus of the solitary tract, the area postrema, the gigantocellular reticular nucleus, and the locus coeruleus contained virus-infected neurons.
PRV-infected neurons that double-stained for nNOS were found in the paraventricular hypothalamic nucleus (PVN), the raphe obscurus nucleus (ROb), the ventromedial medulla (VMM), the rostral ventrolateral medulla (rVLM) and the A5 cell group.
RESULTS: We observed in the fibers and/or the cell bodies located in the dorsal raphe nucleus a total of 14 neuropeptides, 12 in the raphe pallidus, 11 in the medial raphe, 10 in the raphe magnus, 8 in the raphe pontis and 7 in the raphe obscurus.
In the brain, commonly labeled neurons were found in the Al noradrenalin cells/Cl adrenalin cells/caudoventrolateral reticular nucleus, dorsal motor nucleus of vagus nerve, nucleus tractus solitarius, area postrema, raphe obscurus nucleus, raphe pallidus nucleus, raphe magnus nucleus, gigantocellular nucleus, locus coeruleus, parabrachial nucleus, Kolliker-Fuse nucleus, A5 cell group, central gray matter, paraventricular hypothalamic nucleus, lateral hypothalamic nucleus, retrochiasmatic hypothalamic nucleus, bed nucleus of stria terminalis and amygdaloid nucleus.
The areas which were labeled by diffusion of DiI from the nucleus paragigantocellularis lateralis included the arcuate nucleus (ARC) of the medulla, caudal raphe (nucleus raphe obscurus and pallidus), hilum and amiculum of the inferior olive, bilateral "reticular formation" (including the nucleus paragigantocellularis lateralis, nucleus gigantocellular-is and the intermediate reticular zone (IRZ)).
We investigated the behavioral correlates of the activity of serotonergic and non-serotonergic neurons in the nucleus raphe pallidus (NRP) and nucleus raphe obscurus (NRO) of unanesthetized and unrestrained cats.
Experiments were carried out in urethane-anaesthetised rats to investigate whether GABA is involved in mediating inhibition of neuronal activity in the dorsal half of the periaqueductal grey matter (PAG) after stimulation of the serotonin-containing projection to the PAG from nucleus raphe obscurus (NRO).
Phrenic nerve efferent activity and up to 30 single medullary neurones were recorded simultaneously in nucleus tractus solitarii (NTS) including the dorsal respiratory group (DRG), Botzinger-ventral respiratory group (Böt-VRG), and nucleus raphe obscurus of nine adult cats, anaesthetized, injected with a neuromuscular blocking agent, vagotomized and artificially ventilated. Fourteen of twenty-one raphe obscurus neurones with control firing rates less than 4 Hz had significant long-term increases in activity.
Slide-mounted brainstem sections, incubated in [ (125)I]BHSP and then exposed to film, have shown [ (125)I]BHSP binding throughout many brainstem nuclei and tracts, including the ambigual/periambigual (nAmb), dorsal motor vagal (dmnv), gigantocellular (nGC), hypoglossal (nHyp), medial parabrachial (nPBM), lateral reticular (nRL), raphe magnus (nRMg), raphe obscurus (nROb) and solitary tract (nTS) nuclei.
Using immunohistochemistry for the serotonin synthesizing enzyme, tryptophan hydroxylase, we investigated the serotonergic median raphe nuclei (dorsal raphe nucleus, superior central nucleus, and raphe obscurus nucleus) in brains of an older (n = 12; age range 62-84 years) and a younger group (n = 10; age range 5-29 years).
Since raphe pallidus and raphe obscurus both send serotonergic projections to the NTS, we have investigated a neuromodulatory role for these structures on the cardiopulmonary reflex. Excitatory chemical stimulation in the region of raphe pallidus, but not raphe obscurus, attenuated significantly the respiratory and bradycardic components of the cardiopulmonary reflex.
By P1, two separate SP-immunoreactive cell clusters could be recognized at the midline, representing dorsally the nascent raphe pallidus and ventrally the raphe obscurus.
Thyrotropin-releasing hormone (TRH) synthesized in medullary raphe pallidus (Rpa), raphe obscurus (Rob) and the parapyramidal regions (PPR) regulates vagal and sympathetic preganglionic motoneurons.
raphe obscurus, n.
Involvement of the caudal raphe nuclei (raphe pallidus, RPa; raphe magnus, RMg, and raphe obscurus, ROb) in feeding behavior of adult rats was studied by measuring c-Fos protein expression, in animals submitted to the "meal-feeding" model of food restriction in which the rats were fed ad libitum only from 7:00 to 9:00 h, for 15 days.
When neuronal activation at pressor or depressor sites in the anterior hypothalamus was combined with retrograde tracing from the rostral ventrolateral medulla, nucleus raphe magnus and/or nucleus raphe obscurus the majority of double-labelled neurons were located in the caudal half of the periaqueductal gray.
Extensive decreases in the densities of 5-HT-immunoreactive fibers were detected in the lateral septal nucleus, the thalamus, the medial mammillary nucleus, the dorsal and the median raphe nuclei, the raphe obscurus nucleus, the tegmental area, the cerebellum and the vestibular nucleus, though only a small decrease was detected in the inferior colliculus.
The numbers of Fos-like IR positive neurons in the raphe pallidus, raphe obscurus, and parapyramidal regions, which were low in euthyroid rats (0-2/section), increased remarkably as the hypothyroidism progressed and were negatively correlated with serum T(4) levels.
In the medulla, serotonin (5-HT)-immunoreactive neurons of the caudal raphe nuclei, substance P (SP)-immunoreactive neurons of the raphe obscurus (ROb) nuclei and tyrosine hydroxylase (TH)-immunoreactive neurons of A5 cells were infected.
Fos positive cells were additionally observed in the lateral paragigantocellular and gigantocellular reticular nuclei, in the medullary midline complex, in the raphe pallidus and in the raphe obscurus.
We used in vitro autoradiography to identify the endothelin-1 receptor subtype(s) in the nucleus raphe obscurus of rats. In addition, we examined the effects of the endothelin receptor antagonists FR 139317 (endothelin ET(A) receptor-selective antagonist), SB 209670 (endothelin ET(A)/ET(B) receptor-non-selective antagonist) and BQ-788 (endothelin ETB receptor-selective antagonist) on the blood pressure responses following administration of endothelin-1 into the nucleus raphe obscurus. This was decreased in a dose-dependent manner by endothelin-1 (0.1, 1 and 10 pmol) microinjected into the nucleus raphe obscurus. Decreases in blood pressure induced by endothelin-1 were greatly reduced by pre-administration to the nucleus raphe obscurus of FR139317 (5 nmol/rat) or SB209670 (3 nmol/rat; 97+/-7% and 95+/-6%, P < 0.01, n = 5, respectively), but were not affected by BQ-788 (50 nmol/rat; 8+/-3%, P > 0.05, n7 = 5). The antagonists did not influence heart rate when injected to the nucleus raphe obscurus prior to endothelin-1. Therefore, the autoradiographic study showed that there are binding sites for ET-1 within the nucleus raphe obscurus of rats, which are predominantly of ET(A) type.
Quantitative analysis indicated differences in the level of trkB labelling between bulbospinal cells in different brainstem areas, with the highest levels seen in the locus coeruleus and magnocellular portion of the red nucleus, and the lowest levels seen in the medial and superior vestibular nuclei and the raphe obscurus.
raphe obscurus.
Up to 28 neurons distributed in the rostral and caudal ventral respiratory group, nucleus tractus solitarius, and raphe obscurus were recorded simultaneously with microelectrode arrays.
pontis oralis, pars medialis and pars lateralis; raphe obscurus; raphe pallidus; raphe magnus; and raphe pontis.
subcoeruleus pars alpha, raphe obscurus, raphe pallidus, raphe magnus, and locus coeruleus.
Medullary pro-TRH messenger RNAs (mRNAs) were mainly located in the raphe pallidus and raphe obscurus neurons as shown by in situ hybridization and were significantly increased by 70% and 160-230% by Northern blot analyses in 24 h fasted rats at 1 and 3-5 weeks after thyroidectomy, respectively, when serum T4 levels were reduced by 75-87%.
In the control rats, CTb-positive cells were observed in the nucleus reticularis gigantocellularis, nucleus reticularis magnocellularis, nucleus raphe magnus, nucleus raphe obscurus, and nucleus raphe pallidus.
Neurones were monitored with microelectrode arrays in two or three of the following domains: nucleus raphe obscurus-nucleus raphe pallidus, nucleus raphe magnus, and rostral and caudal ventrolateral medulla.
Previous physiological and behavioral studies have shown that the nucleus raphe obscurus (nRO) modulates pelvic floor reflex function (Yamanouchi and Kakeyama [ 1992] Physiol.
In the other two important hindbrain nuclei controlling gastric function, the nucleus raphe obscurus and nucleus ambiguus, bicuculline (353 pmol) significantly increased intragastric pressure via vagally mediated pathways.
Diamidino Yellow and Fast Blue injections into the right and left PML, respectively, resulted in labelling of a limited number of these neurones exclusively within the raphe pallidus and raphe obscurus nuclei..
Therefore, we recorded unitary excitatory postsynaptic currents (EPSCs) in caudal raphe neurones (raphe obscurus and pallidus) following local electrical stimulation in a neonatal rat brainstem slice preparation; most neurones (79 %; n = 72/91) recovered following post hoc immunohistochemistry were tryptophan hydroxylase-immunoreactive, indicating that they were serotonergic.
Serotonergic neurons of the medulla oblongata (nucleus raphe obscurus and nucleus raphe pallidus), which provide a major projection to sympathetic and motor output systems, receive a catecholaminergic input and express alpha 2-adrenergic receptors.
Neurons double-labeled for GABA and MOR1 were present in hippocampus and NRD, as well as in olfactory bulb, dorsal lateral periaqueductal gray matter, nucleus raphe medianis, nucleus raphe obscurus, and the spinal trigeminal nucleus and tract.
raphe obscurus, and n.
Therefore, we investigated the effects of microinjection of VIP in the dorsal vagal complex (DVC), nucleus raphe obscurus (nROb) and nucleus ambiguus of alpha-chloralose-anesthetized rats while recording intragastric pressure, pyloric and greater curvature smooth muscle contractile activity, blood pressure and heart rate.
Consistent with this hypothesis, virtually all serotonergic neurons within the medullary nuclei raphe obscurus and raphe pallidus in cats are activated in response to specific motor challenges.
In the present study, anterograde tracing of descending pathways originating from the caudal nucleus raphe obscurus (nRO) revealed that this nucleus projects to cells within the intermediolateral (IML) cell column of the thoracic cord and the sacral parasympathetic nucleus (SPN).
Thyrotropin-releasing hormone (TRH) from the nucleus raphe obscurus (nROb) innervates the dorsal vagal complex (DVC) and activates gastric motor function.
The present study was carried out as a first stage in establishing whether the ventrolateral PAG may exert these influences after a relay in the caudal medullary raphe nuclei (nucleus raphe obscurus and nucleus raphe pallidus).
Pituitary adenylate cyclase-activating polypeptide (PACAP)-like immunoreactive cell bodies and fibers are visualized in hindbrain nuclei that are involved in the regulation of autonomic function, yet little is known about the gastric and cardiovascular effects of this peptide in the dorsal vagal complex, nucleus raphe obscurus, and nucleus ambiguus. Microinjections of PACAP-38 (10 and 100 pmol) into each of the nuclei significantly increased peak intragastric pressure, but the total area of the response was only significantly increased by the highest dose (100 pmol) in the case of the dorsal vagal complex and nucleus raphe obscurus. Bilateral vagotomy abolished the increase in intragastric pressure in response to microinjection of PACAP-38 into the dorsal vagal complex and nucleus raphe obscurus. We conclude that PACAP-38 in the dorsal vagal complex and nucleus raphe obscurus is involved in vagally mediated gastric motor excitation..
The percentages of 5-HT-ir neurons containing 5-HT(1A)R-ir were 28% in RPa, 18% in PPR, and 31% in raphe obscurus.
We used whole cell current- and voltage-clamp recording in neonatal rat brain stem slices to characterize firing properties and effects of serotonin (5-HT) on neurons (n = 225) in raphe pallidus (RPa) and raphe obscurus (ROb).
Sixty to seventy-two hours after virus injection in both 2- and 12-day-old rats, infected neurons were detected in Barrington's nucleus, nucleus paragigantocellularis, nucleus reticularis gigantocellularis, A5 area, nucleus raphe obscurus, locus subcoeruleus, periaquaductal gray, red nucleus, paraventricular nucleus and cerebral cortex.
We report that nucleus raphe obscurus stimulation not only abolishes phrenic nerve activity, but also hyperpolarizes the membrane potential, depresses periodic synaptic drive potentials and thus action potential discharges in caudal medullary expiratory neurons.
When animals were subjected to a novel environment (moderate stimulation), additional NO-producing neurons were activated in the medial septum, medial amygdala, hypothalamic nuclei (lateral, periventricular, and posterior), colliculi, nucleus raphe obscurus, medial vestibular nucleus, nucleus of the tractus solitarius, and several components of the ventrolateral medulla.
In another series of experiments L-glutamate (0.2 M) was microinjected (75 to 150 nl) into the nucleus raphe obscurus. Pressor responses were also predominant in paralyzed animals (delta = +15 to +95 mmHg; 47% of the stimulated sites), and after microinjection of L-glutamate into the raphe obscurus (A = +20 to +45 mmHg).
At E18 fibers from the parafascicular prerubral nucleus, the interstitial nucleus of Cajal, the mesencephalic reticular nucleus, the caudal pontine reticular nucleus, the laterodorsal tegmental nucleus, the subcoerulean nucleus, the spinal vestibular nucleus, the interpolar spinal trigeminal nucleus, the raphe obscurus nucleus and the ventral medullary reticular nucleus arrived in the lumbosacral cord.
There is a dense serotonergic projection from nucleus raphe pallidus and nucleus raphe obscurus to the trigeminal motors nucleus and serotonin exerts a strong facilitatory action on the trigeminal motoneurons.
We have recently described a vagally mediated gastric relaxation evoked by micro-injection of substance P (SP) into the nucleus raphe obscurus (NRO).
In male urethane-anaesthetized rats, activation of neurons in nucleus raphe obscurus and the caudal tip of nucleus raphe magnus by microinjection of 50-100 nl 0.1 M D,L-homocysteic acid produced a 75.6 +/- 5.2% reduction in the firing rate in 25 neurons in the lateral and dorsolateral sectors of the periaqueductal gray matter which lasted for 102.3 +/- 13.3s (mean +/- S.E.M.).
The dorsal vagal complex (DVC) and nucleus raphe obscurus (nROb) are currently known to control vagal outflow to the stomach and the pancreas.
A dense network of immunoreactive neurons and fibres was present in the nucleus raphe obscurus, lateral reticular nucleus and parvocellular lateral reticular nucleus.
We have previously shown that substance P (SP), microinjected into the caudal nucleus raphe obscurus (nROb) of the rat decreases intragastric pressure via a vagally mediated pathway.
Nucleus raphe obscurus (NRO) and dorsal periaqueductal grey (dPAG) were stimulated singly or simultaneously by square-wave pulses to induce the Fos-expression in midbrain and medulla oblongata.
The effects of endogenously released 5-HT were also studied by chemical stimulation of neurons within the raphe obscurus. 05); or (3) endogenously released in response to activation of neurons within the raphe obscurus via pressure injection of (R,S)- "alpha"-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA, 34 +/- 15%; P < 0.05) or 5-HT (33 +/- 5%; P < 0.
In another series of experiments L-glutamate (0.18 M) was microinjected (75 to 150 nl) into the nucleus raphe obscurus. Pressor responses were also predominant in paralyzed animals (delta = +15 to +95 mmHg; 62.5% of the stimulated sites), and after microinjection of L-glutamate into the raphe obscurus (delta = +35 to +135 mmHg).
On E20 and P0, labeling appeared in the dorsal column, laterodorsal tegmental, raphe obscurus, parvocellular reticular, ventral gigantocellular reticular, and parahypoglossal nuclei, and laminae IX of the cervical spinal cord.
In some cases, one or two double labeled neurons were detected in the lateral hypothalamic area and nucleus raphe obscurus.
The microinjection of L-glutamate (1-6 nmol/rat) and N-methyl-D-aspartate (NMDA 1-10 nmol/rat), ionotropic glutamate receptor (iGluR) agonists, into the nucleus raphe obscurus caused a concentration -dependent increase of arterial blood pressure. These observations indicate opposing roles for ionotropic and metabotropic receptors in the glutamate-induced blood pressure changes elicited from the nucleus raphe obscurus.
Forty-five cells recorded in the raphe obscurus and pallidus nuclei were antidromically activated with latencies characteristic of non-myelinated fibres (4.4-42.0 ms).
Stimulation of either peripheral chemoreceptors or nucleus raphe obscurus results in long-term facilitation of phrenic motoneurone activity. The first objective of this work was to measure the concurrent responses of neurones in the nucleus raphe obscurus, the nucleus tractus solitarii, and the regions of the retrofacial nucleus, nucleus ambiguus and nucleus retroambigualis during induction of long-term facilitation. One hundred and thirteen of 348 neurones were monitored in the nucleus raphe obscurus.
In this study of the brainstem in laboratory rats, a transient expression is also observed in the rubrospinal tract, parvocellular reticular nucleus, raphe obscurus, cuneate and gracile nuclei, and the ventral median fissure of the spinal cord.
More specifically, the increase of electrical activity of serotonergic neurons in raphe obscurus has been correlated with locomotion in treadmill-trained cats [ Jacobs, B.L.
These responses were attenuated significantly after microinjection of 200 nl 0.1 M DL-homocysteic acid (DLH) into nucleus raphe magnus (NRM, n = 12) or nucleus raphe obscurus (NRO, n = 22).
Stimulation of the nucleus raphe obscurus (nRO) by kainic acid (423 pmol/10 nol) produced marked release of serotonin into dorsal medullary dialysates containing the DVC in freely fed, but no 24-h fasted rats.
In adult rats, serotonin transporter mRNA labelled neurons were detected in the nucleus raphe obscurus, pallidus and magnus.
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.
Serotonergic neuronal responses during three specific motor activities were studied in nuclei raphe obscurus (NRO) and raphe pallidus (NRP) of freely moving cats by means of extracellular single-unit recordings.
5-HT neurons of the caudal raphe nuclei (raphe pallidus, raphe obscurus, and raphe magnus) were labeled; some of these contained substance P or TRH-immunoreactivity with an occasional neuron staining for all three putative neurotransmitters.
PYY (200 ng) microinjected into the raphe pallidus, raphe obscurus, and nucleus ambiguous also increased GAS, although the response was of shorter duration than that in the DMN.
Because the nucleus raphe obscurus (NRO) maintains anatomic connections via the DVC to the pancreas, a functional significance of these findings was investigated in the present study.
Our results showed the presence of HRP/ChAT double-labelled neurons in (1) the midline medulla: the periventricular gray beneath the 4th ventricle, C3 adrenergic area, raphe obscurus nucleus and medial longitudinal fasciculus, (2) the reticular formation: the medullary, lateral, intermediate, gigantocellular, lateral paragigantocellular and dorsal paragigantocellular reticular nuclei and gigantocellular reticular nucleus ventralis, and (3) sensory nuclei: the gracile nucleus, cuneate nucleus, external cuneate nucleus, spinal trigeminal nucleus interpolaris, prepositus hypoglossal nucleus and medial vestibular nucleus.
A particularly dense projection to widespread regions of the ventral medulla was traced from the raphe obscurus. The diffuse and dense intramedullary connections of the raphe obscurus suggest that it might have an important role in coordinating the activity of rostral ventral medullary cells.
The possibility was explored that raphe-spinal neurons with myelinated axons arising in the rostral part of raphe obscurus provide excitatory drive to sympathetic neurons. It is concluded that some cell bodies located in rostral raphe obscurus that project to the spinal cord relay excitatory drive to sympathetic neurons..
Antinociception was induced by beta-endorphin (0.6 nmol) given into nucleus raphe obscurus and was assessed by the tail-flick test in pentobarbital-anesthesized rats.
Of all the serotonin cell groups in the brainstem, the nucleus raphe magnus contained the most double-labelled cells (a mean of 3.6% of a total of 625-1155 serotonin-immunoreactive cells counted in this nucleus), followed by the nucleus raphe obscurus (1.5% of a total of 220-550 serotonin-immunoreactive neurons counted). These results suggest that only a very small percentage of serotonergic neurons in the medullary raphe nuclei (raphe magnus and raphe obscurus) also contain GABA, whereas such cells are virtually absent in the midbrain raphe nuclei or in the non-raphe serotonergic cell groups in the brainstem..
The existence of an interaction between serotonin (5-HT) and thyrotropin-releasing hormone (TRH) in the nucleus raphe obscurus (NRO) of the rat in their excitatory effects on gastric motor function was examined using two different approaches.
We have recently shown that microinjection of substance P (SP) into the nucleus raphe obscurus (NRO) of the rat decreases intragastric pressure, whereas microinjection of serotonin (5-HT) increases it.
Of those recorded 26 were in the region of raphe obscurus, nine in raphe pallidus and one in raphe magnus.
Subpopulations of raphe pallidus (Rpa) and raphe obscurus (Rob) neurons containing TRH, serotonin (5-HT), and substance P contribute projections to the dorsal vagal complex (DVC).
Lower densities of labelled perikarya were found after the microinjection of [ 3H]GABA, and the only regions in which a small number of cells were labelled by both D-[ 3H]aspartate and [ 3H]GABA were trigeminal nucleus, reticular nuclei and raphe obscurus.
raphe obscurus-n.
In situ hybridization histochemistry showed that the increase in silver grain density occurred exclusively in the raphe pallidus and raphe obscurus.
The inhibition was blocked after microinjections of 500-1000 nl local anaesthetic (4% lignocaine, n = 9) or 0.2 M glycine (n = 4) into nucleus raphe obscurus (NRO).
In rats exposed to cold (4 degrees C) restraint for 3 h, numerous Fos-positive nuclei were observed in the dorsal motor nucleus of the vagus, raphe pallidus, locus coeruleus, and paraventricular nucleus of the hypothalamus, and, to a lesser extent, in the raphe obscurus, parapyramidal region, and medullary noradrenergic region, bed nucleus of the stria terminalis and septum.
Both components of the response were attenuated following microinjection of 200 nl 0.1 M D,L-homocysteic acid into the caudal pole of the nucleus raphe magnus (NRM; n = 12) and into the nucleus raphe obscurus (NRO; n = 22) to selectively activate neuronal perikarya.
The purpose of this study was to investigate whether there exists a functional interaction between thyrotropin-releasing hormone (TRH) and substance P (SP) in the nucleus raphe obscurus (NRO) in their effects on gastric motor function.
Retrograde transport of rhodamine- or coumarin-labelled latex microspheres was used to investigate projections from nucleus raphe obscurus (NRO) to the periaqueductal grey matter (PAG) in rats.
High binding densities were seen over subnuclei of the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, the intermediate reticular zone, the gigantocellular and dorsal paragigantocellular nuclei, and the raphe obscurus nucleus.
Among the bulbospinal neurons encountered within individual 5-HT-rich medullary nuclei, high proportions of these neurons co-containing serotonin and methionine enkephalin were evidenced in the nucleus raphe obscurus (64%) and nucleus raphe pallidus (56%), less so in cell group B1/3 (41%), nucleus raphe magnus (39%), and the nucleus reticularis magnocellularis (29%).
Using this triple-label approach, we found that virtually all medullary serotonergic cells (raphe pallidus, raphe obscurus and parapyramidal area) including those with identified spinal projections contain punctate alpha 2A-AR-LIR.
In addition, the medial nucleus receives projections from the superior central nucleus, the nucleus raphe obscurus, the nucleus raphe magnus, and the periolivary reticular formation.
Postnatal changes in TRH expression in nucleus (n.) raphe obscurus (ROb) and n.
The following nuclei of the medulla receive moderately dense projections from the DR: nucleus gigantocellularis, nucleus raphe magnus, nucleus raphe obscurus, facial nucleus, nucleus gigantocellularis-pars alpha, and the rostral ventrolateral medullary area.
of the nucleus raphe dorsalis) and fibres; however, 5HTP-immunostaining remained in perikarya of the nuclei centralis superior and raphe obscurus.
Double-labeled neurons (rhodamine beads plus substance P immunoreactivity) were found in the midline caudal raphe nuclei (raphe obscurus, raphe pallidus, and raphe magnus) and in the ventrolateral medulla in the parapyramidal region.
The dorsal and median raphe nuclei contained intensely labeled neurons, while the caudal linear nucleus, raphe magnus nucleus, raphe pontis nucleus, raphe pallidus nucleus and the raphe obscurus nucleus contained weakly or moderately labeled neurons.
Neurons were located in the nucleus raphe magnus (79%) and the nucleus raphe obscurus (15%).
Little is known about the functional role of putative neurotransmitters in the nucleus raphe obscurus (NRO) in the control of gastric motor function, although thyrotropin-releasing hormone (TRH) and substance P (SP) have been detected in the cell bodies and/or fibers of this nucleus.
A total of 26 respiratory neurons, whose spikes were confirmed to originate from the cell bodies, was recorded in the raphe obscurus and pallidus.
The results indicated: (1) The nucleus raphe magnus, nucleus raphe pallidus, and nucleus raphe obscurus contained 5-HT neurons projecting to the Vm, VII or XII.
No NADPH diaphorase activity was detected in serotoninergic neurons in the medullary nuclei (including the raphe magnus, raphe pallidum, and raphe obscurus).
Electrical stimulation of the nucleus raphe obscurus (NRO) in urethane-anesthetized rats increases arterial blood pressure (BP) between 20 and 95 mmHg (mean, 61.14 +/- 6.57; N = 30).
A moderate to strong labelling was also present within the paraventricular hypothalamic nucleus, the arcuate nucleus, the nucleus raphe magnus, the nucleus raphe obscurus and the locus coeruleus.
In the present study, we examined whether neurons in the nucleus raphe obscurus (NRO) played a significant role in the formation of gastric ulcers with the use of Sprague-Dawley rats. It was also demonstrated that kainic acid injection outside the raphe obscurus boundaries failed to develop gastric lesions. All these results suggest, for the first time, that excitation of neurons in the medullary raphe obscurus induces gastric ulceration through vagal stimulation..
The purpose of the present study was to investigate the effect of microinjection of serotonin (5-HT) and selected 5-HT receptor subtype agonists and antagonists into the caudal nucleus raphe obscurus on gastrointestinal motor activity in urethane-chloralose anesthetized rats. These results indicate that 5-HT activates gastric motor function in the caudal nucleus raphe obscurus via a vagally mediated pathway and that the activation of multiple 5-HT receptor subtypes is required for the gastric excitatory effect of 5-HT..
Selective activation of neuronal perikarya in nucleus raphe obscurus (NRO) by microinjection of 50-100 nl D,L-homocysteic acid (DLH) inhibited ongoing activity of 25/31 neurones tested in the PAG for periods of 30-580 s, mean 183.5 s.
In the medulla, light to moderately densely labeled cells were scattered in the nucleus of Probst's bundle, the medial vestibular nucleus, the lateral reticular nucleus, and the raphe obscurus nucleus.
The duration of the inhibition was reduced by 51.1% after microinjection of GABA (40-160 nmol in volumes of 200-400 nl, 9/12 sites), but not 165 mM NaCl (8/8 sites) in nucleus raphe magnus (NRM) and the rostral half of nucleus raphe obscurus (NRO).
Microinjections of vehicle or RX 77368 into the raphe pallidus or raphe obscurus were performed using pressure injection of 50 nl through glass micropipettes 30 min following basal recording of gastric contractility. RX 77368 (0.7-77 pmol) dose dependently stimulated gastric contractility when microinjected into the raphe pallidus and raphe obscurus. The stimulation of gastric contractions induced by microinjection of RX 77368 (77 pmol) into these raphe nuclei was completely blocked by vagotomy and prevented (raphe obscurus) or reduced (raphe pallidus) by atropine.
Male Long-Evans rats were implanted with cannulae terminating in the region of the nucleus raphe obscurus/inferior olive, through which they received injections of DOI (0.1-10 micrograms).
The results confirm the brainstem projections to the MPA from the central grey matter, ventral tegmental area, subcoeruleus area, the dorsal raphe nucleus, the lateral parabrachial nucleus, the raphe pontis nucleus, the raphe obscurus nucleus, the region of the paragigantocellular nucleus and the nucleus of the solitary tract.
raphe obscurus-n.
raphe obscurus, n.
Male sexual activities were tested in androgen-treated castrated male rats with lesions of the raphe obscurus nucleus (ROBL) or lesions of the raphe magnus nucleus (RMGL). The results suggest that the raphe obscurus nucleus is involved in the neural mechanisms mediating copulatory behavior in male rats, and that the raphe magnus nucleus is not. In several castrated control and ROBL males, serotonin-synthesis inhibitor, p-chlorophenylalanine (PCPA) was injected before the behavioral test, because the raphe obscurus nucleus contains a large number of serotonergic neuronal cells. Moreover, PCPA acts on serotonergic neurons other than those in the raphe obscurus nucleus, thereby facilitating mount activities..
By electrical stimulation of or microinjection of L-glutamate into nucleus raphe obscurus (NRO), the following results were observed: (1) A long stimulus train (50-200 microA, 100Hz, 4-6 s) delivered to NRO resulted in a decrease in integrated phrenic amplitude (IPA) or complete cessation of phrenic nerve discharge.
RX 77368 (77 pmol) increased 5-HT release after microinjection into the raphe obscurus, raphe pallidus, and nucleus ambiguus, although the responses were significantly lower compared with that induced by DVC microinjection.
No somata in the brainstem raphe nuclei, including raphe obscurus and raphe magnus, were observed to bind riboprobe.
Substantial cerebellar projections originated from most of the various presumed serotonergic brainstem raphe cell groups (particularly raphe obscurus in the medulla), as well as from the presumed cholinergic Ch5 cell group (the pedunculopontine pars compactus nucleus).
The conditioning stimuli were applied either within the ipsilateral locus coeruleus/subcoeruleus or outside these nuclei (in the raphe magnus, raphe obscurus, or cuneiform nuclei).
Specific and saturable retrograde labeling was also observed within other NGF receptor-bearing neurons, including the prepositus hypoglossal nucleus and the raphe obscurus nucleus.
Neurons were located in raphe magnus (RM, 65%), raphe obscurus (RO, 32%), and raphe pallidus (RPa, 4%).
The cell bodies are largely confined to the midline (raphe) region of the brain stem in two general clusters: a superior group that consists of the dorsal raphe nucleus (B-7 and B-6), median raphe nucleus (B-8 and B-5), caudal linear nucleus (rostral B-8), and supralemniscal nucleus (B-9), and an inferior group that consists of nucleus raphe obscurus (B-2), nucleus raphe pallidus (B-1), nucleus raphe magnus (B-3), ventral lateral medulla (B-1/B-3), and the area postrema.
By means of dual immunohistochemical labeling on the same brain section examined with a light microscope, the present study reports the presence with serotonin (5-hydroxytryptamine; 5-HT) of gamma-aminobutyric acid (GABA), substance P (SP), thyrotropin-releasing hormone (TRH), leucin-enkephalin (LEU-enk), or methionine-enkephalin (MET-enk), within the same neuron in the nuclei raphe magnus, raphe obscurus, and raphe pallidus of the rat.
We found that Enk projections to the ILp nucleus are found in such serotonergic-containing areas as the raphe obscurus; raphe pallidus; gigantocellular reticular nucleus, pars alpha; paragigantocellular lateral nucleus; raphe magnus; and the rostral extension of the raphe magnus nucleus.
The major components of the ventromedial funiculus include projections from the medullary reticular formation, pontine reticular formation, raphe obscurus and pallidus, lateral vestibular nucleus, and interstitial nucleus, and to a minor extent from the locus coeruleus, lateral hypothalamus, and nucleus periventricularis hypothalami.
By using double-labeling techniques accomplished by retrograde transport of Fluoro-Gold following microinjection into the dorsal motor nucleus/nucleus of the solitary tract combined with immunohistochemistry for thyrotropin-releasing hormone, it was demonstrated that thyrotropin-releasing hormone-immunoreactive neurons projecting to the dorsal motor nucleus/nucleus of the solitary tract reside in the nucleus raphe pallidus, nucleus raphe obscurus, and the parapyramidal region of the ventral medulla, but not in the paraventricular nucleus of the hypothalamus.
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