Activation of slowly conducting medullary raphé-spinal neurons, including serotonergic neurons, increases cutaneous sympathetic vasomotor discharge in rabbit

2005 ◽  
Vol 288 (4) ◽  
pp. R909-R918 ◽  
Author(s):  
Youichirou Ootsuka ◽  
William W. Blessing

Neurons in the rostral medullary raphé/parapyramidal region regulate cutaneous sympathetic nerve discharge. Using focal electrical stimulation at different dorsoventral raphé/parapyramidal sites in anesthetized rabbits, we have now demonstrated that increases in ear pinna cutaneous sympathetic nerve discharge can be elicited only from sites within 1 mm of the ventral surface of the medulla. By comparing the latency to sympathetic discharge following stimulation at the ventral raphé site with the corresponding latency following stimulation of the spinal cord [third thoracic (T3) dorsolateral funiculus] we determined that the axonal conduction velocity of raphé-spinal neurons exciting ear pinna sympathetic vasomotor nerves is 0.8 ± 0.1 m/s ( n = 6, range 0.6–1.1 m/s). Applications of the 5-hydroxytryptamine (HT)2A antagonist trans-4-((3 Z)3-[(2-dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl)propen-1-yl)-phenol, hemifumarate (SR-46349B, 80 μg/kg in 0.8 ml) to the cerebrospinal fluid above thoracic spinal cord (T1-T7), but not the lumbar spinal cord (L2-L4), reduced raphé-evoked increases in ear pinna sympathetic vasomotor discharge from 43 ± 9 to 16 ± 6% ( P < 0.01, n = 8). Subsequent application of the excitatory amino acid (EAA) antagonist kynurenic acid (25 μmol in 0.5 ml) substantially reduced the remaining evoked discharge (22 ± 8 to 6 ± 6%, P < 0.05, n = 5). Our conduction velocity data demonstrate that only slowly conducting raphé-spinal axons, in the unmyelinated range, contribute to sympathetic cutaneous vasomotor discharge evoked by electrical stimulation of the medullary raphé/parapyramidal region. Our pharmacological data provide evidence that raphé-spinal neurons using 5-HT as a neurotransmitter contribute to excitation of sympathetic preganglionic neurons regulating cutaneous vasomotor discharge. Raphé-spinal neurons using an EAA, perhaps glutamate, make a substantial contribution to the ear sympathetic nerve discharge evoked by raphé stimulation.

1997 ◽  
Vol 77 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Susan M. Barman ◽  
Gerard L. Gebber

Barman, Susan M. and Gerard L. Gebber. Subgroups of rostral ventrolateral medullary and caudal medullary raphe neurons based on patterns of relationship to sympathetic nerve discharge and axonal projections. J. Neurophysiol. 77: 65–75, 1997. This study was designed to answer three questions concerning rostral ventrolateral medullary (RVLM) and caudal medullary raphe (CMR) neurons with activity correlated to sympathetic nerve discharge (SND). 1) What are the proportions of RVLM and CMR neurons that have activity correlated to both the cardiac-related and 10-Hz rhythms in SND, to only the 10-Hz rhythm, and to only the cardiac-related rhythm? 2) Which of these cell types project to the spinal cord? 3) Do the outputs of the cardiac-related and 10-Hz rhythm generators converge at the level of bulbospinal neurons or their antecedent interneurons? To address these issues we recorded from 44 RVLM and 48 CMR neurons with sympathetic nerve–related activity in urethan-anesthetized cats with intact carotid sinus nerves, but sectioned aortic depressor and vagus nerves. Spike-triggered averaging, arterial pulse-triggered analysis, and coherence analysis revealed that the naturally occurring discharges of 24 of these RVLM neurons and 41 of these CMR neurons were correlated to both the 10-Hz and cardiac-related rhythms in inferior cardiac postganglionic SND. The discharges of the other neurons were correlated to only the 10-Hz rhythm (15 RVLM and 6 CMR neurons) or to only the cardiac-related rhythm (5 RVLM neurons and 1 CMR neuron) in SND. The time-controlled collision test verified that 16 of 18 RVLM and 31 of 34 CMR neurons with activity correlated to both rhythms were antidromically activated by stimulation of the white matter of the first thoracic (T1) segment of the spinal cord. In contrast, only 1 of 10 RVLM neurons and 0 of 4 CMR neurons with activity correlated to only the 10-Hz rhythm could be antidromically activated by stimulation at T1. Also 0 of 3 RVLM neurons with activity correlated to only the cardiac-related rhythm in SND were antidromically activated by spinal stimulation. These data show for the first time that bulbospinal sympathetic pathways emanating from the RVLM and CMR are comprised almost exclusively of neurons whose discharges are correlated to both the cardiac-related and 10-Hz rhythms in SND. Moreover, the data support the hypothesis that the outputs of the cardiac-related and 10-Hz rhythm generators converge on RVLM and CMR bulbospinal neurons rather than on their antecedent interneurons. Finally, the data demonstrate that a substantial proportion of RVLM neurons and a small group of CMR neurons with activity correlated to SND do not project to the thoracic spinal cord. Their discharges were correlated to only one of the rhythms in SND. Their axonal trajectories and functions are unknown.


1991 ◽  
Vol 261 (2) ◽  
pp. R393-R402 ◽  
Author(s):  
D. H. Huangfu ◽  
N. Koshiya ◽  
P. G. Guyenet

Unit recording experiments were designed to determine whether A5 noradrenergic neurons contribute to the generation of the splanchnic sympathetic nerve discharge (SSND) of halothane-anesthetized rats. Neurons (presumed A5 cells) were selected on the following bases: location in the ventrolateral tegmentum rostrolateral to facial nucleus (FN), antidromic (AD) activation from thoracic spinal cord, and complete inhibition by clonidine (10-15 micrograms/kg iv). These cells (n = 59) had low rates of spontaneous firing (1.4 +/- 0.2 spikes/s) and slow conduction velocities (2.6 +/- 0.2 m/s). The AD activation of seven of eight neurons was abolished within 1 h after intraspinal microinjection of 6-hydroxydopamine (4 micrograms), but the drug failed to affect the AD responses of eight sympathoexcitatory cells located caudal to the FN (control cells). The terminal fields of 16 A5 area neurons were found in the intermediolateral cell column of the spinal cord. Most neurons (63%, 37/59) were inhibited by raising arterial pressure and by train stimulation of the aortic depressor nerve (ADN, 47%, 9/20). A few cells responded to ADN stimulation but not to arterial pressure elevation or vice versa. The discharge of the cells was correlated to the SSND and preceded a peak of SSND by 69 +/- 6 ms (12/29 in intact and 3/9 in debuffered rats). We conclude that 40% of A5 cells may have a visceral vasomotor sympathoexcitatory function.


2018 ◽  
Vol 314 (3) ◽  
pp. G341-G348 ◽  
Author(s):  
Hiroyuki Nakamori ◽  
Kiyotada Naitou ◽  
Yuuki Horii ◽  
Hiroki Shimaoka ◽  
Kazuhiro Horii ◽  
...  

Colorectal motility is regulated by two defecation centers located in the brain and spinal cord. In previous studies, we have shown that administration of serotonin (5-HT) in the lumbosacral spinal cord causes enhancement of colorectal motility. Because spinal 5-HT is derived from neurons of the medullary raphe nuclei, including the raphe magnus, raphe obscurus, and raphe pallidus, we examined whether stimulation of the medullary raphe nuclei enhances colorectal motility via the lumbosacral defecation center. Colorectal pressure was recorded with a balloon in vivo in anesthetized rats. Electrical stimulation of the medullary raphe nuclei failed to enhance colorectal motility. Because GABAergic neurons can be simultaneously activated by the raphe stimulation and released GABA masks accelerating actions of the raphe nuclei on the lumbosacral defecation center, a GABAA receptor antagonist was preinjected intrathecally to manifest excitatory responses. When spinal GABAA receptors were blocked by the antagonist, electrical stimulation of the medullary raphe nuclei increased colorectal contractions. This effect of the raphe nuclei was inhibited by intrathecal injection of 5-hydroxytryptamine type 2 (5-HT2) and type 3 (5-HT3) receptor antagonists. In addition, injection of a selective 5-HT reuptake inhibitor in the lumbosacral spinal cord augmented the raphe stimulation-induced enhancement of colorectal motility. Transection of the pelvic nerves, but not transection of the colonic nerves, prevented the effect of the raphe nuclei on colorectal motility. These results demonstrate that activation of the medullary raphe nuclei causes augmented contractions of the colorectum via 5-HT2 and 5-HT3 receptors in the lumbosacral defecation center. NEW & NOTEWORTHY We have shown that electrical stimulation of the medullary raphe nuclei causes augmented contractions of the colorectum via pelvic nerves in rats. The effect of the medullary raphe nuclei on colorectal motility is exerted through activation of 5-hydroxytryptamine type 2 and type 3 receptors in the lumbosacral defecation center. The descending serotoninergic raphespinal tract represents new potential therapeutic targets against colorectal dysmotility such as irritable bowel syndrome.


1991 ◽  
Vol 69 (7) ◽  
pp. 1035-1045 ◽  
Author(s):  
John Ciriello ◽  
Michael B. Gutman

The functional projections from pressor sites in the subfornical organ (SFO) were identified using the 2-deoxyglucose (2-DG) autoradiographic method in urethane-anesthetized, sinoaortic-denervated rats. Autoradiographs of brain and spinal cord sections taken from rats whose SFO was continuously stimulated electrically for 45 min with stereotaxically placed monopolar electrodes (150 μA, 1.5-ms pulse duration, 15 Hz) following injection of tritiated 2-DG were compared with control rats that received intravenous infusions of pressor doses of phenylephrine to mimic the increase in arterial pressure observed during SFO stimulation. Comparisons were also made to autoradiographs from rats in which the ventral fornical commissure (CFV), just dorsal to the SFO, was electrically stimulated. The pressor responses during either electrical stimulation of the SFO or intravenous infusion of phenylephrine were similar in magnitude. On the other hand, stimulation of the CFV did not elicit a significant pressor response. Electrical stimulation of the SFO increased 2-DG uptake, in comparison to the phenylephrine-infused rats, in the nucleus triangularis, septofimbrial nucleus, lateral septal nucleus, nucleus accumbens, bed nucleus of the stria terminalis, dorsal and ventral nucleus medianus (median preoptic nucleus), paraventricular nucleus of the thalamus, hippocampus, supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus of the hypothalamus, and the intermediolateral nucleus of and central autonomic area of the thoracic spinal cord. In contrast, in rats whose CFV was stimulated, these nuclei did not demonstrate changes in 2-DG uptake compared with control animals that received pressor doses of phenylephrine. These data have demonstrated some of the components of the neural circuitry likely involved in mediating the pressor responses to stimulation of the SFO and the corrective responses to activation of the SFO by disturbances to circulatory and fluid balance homeostasis.Key words: cardiovascular reflex pathways, drinking, median preoptic nucleus, osmoreceptors, paraventricular nucleus of the hypothalamus, supraoptic nucleus.


1983 ◽  
Vol 50 (4) ◽  
pp. 926-940 ◽  
Author(s):  
W. S. Ammons ◽  
R. W. Blair ◽  
R. D. Foreman

Spinothalamic (ST) neurons in the C8-T5 segments of the spinal cord were examined for responses to electrical stimulation of the left thoracic vagus nerve (LTV). Seventy-one ST neurons were studied in 39 anesthetized monkeys (Macaca fascicularis). Each neuron could be excited by manipulation of its somatic field and by electrical stimulation of cardiopulmonary sympathetic afferent fibers. LTV stimulation resulted in inhibition of the background activity of 43 (61%) ST neurons. Nine (13%) were excited, 3 (4%) were excited and then inhibited, while 16 (22%) did not respond. There was little difference among these groups in terms of the type of somatic or sympathetic afferent input although inhibited cells tended to be more prevalent in the more superficial laminae. The degree of inhibition resulting from LTV stimulation was related, in a linear fashion, to the magnitude of cell activity before stimulation. LTV inhibition of background activity was similar among wide dynamic range, high threshold, and high-threshold cells with inhibitory hair input. Any apparent differences in LTV inhibitory effects among these groups were accounted for by the differences in ongoing cell activity as predicted by linear regression analysis. LTV stimulation inhibited responses of 32 of 32 ST cells to somatic stimuli. In most cases the stimulus was a noxious pinch; however, LTV stimulation also inhibited responses to innocuous stimuli such as hair movement. Bilateral cervical vagotomy abolished the inhibitory effect of LTV stimulation on background activity (six cells) or responses to somatic stimuli (seven cells). Stimulation of the cardiac branch of the vagus inhibited activity of three cells to a similar degree as LTV stimulation, while stimulation of the vagus below the heart was ineffective in reducing activity of 10 cells. We conclude that LTV stimulation alters activity of ST neurons in the upper thoracic spinal cord. Vagal inhibition of ST cell activity was due to stimulation of cardiopulmonary vagal afferent fibers coursing to the brain stem, which appear to activate descending inhibitory spinal pathways. Vagal afferent activity may participate in processing of somatosensory information as well as information related to cardiac pain.


1994 ◽  
Vol 266 (1) ◽  
pp. R257-R267 ◽  
Author(s):  
E. W. Akeyson ◽  
L. P. Schramm

To better understand the spinal transmission of visceral afferent information, we conducted neurophysiological studies of single spinal neurons that receive input from the greater splanchnic nerve (GSN). Extracellular single-neuron recordings were made in the thoracic spinal cord of chloralose-anesthetized, paralyzed, and artificially ventilated rats, some of which had undergone acute spinal transection at C1. Neurons were divided into four classes according to their responses to GSN stimulation: one-burst excitatory, two-burst excitatory, biphasic, and inhibited. We then studied the characteristics of the convergent somatic input to each class of neurons using either natural somatic stimuli or electrical stimulation of the iliohypogastric nerve (IHN). Most splanchnic input was mediated by unmyelinated fibers, whereas somatic input was mediated by both unmyelinated and small myelinated fibers. Most of the neurons exhibited somatic receptive fields, and the majority responded to both innocuous and noxious somatic stimuli. However, a small number could be excited only by GSN stimulation. Although a careful analysis of response characteristics indicated that there was a tendency for neurons to exhibit similar responses to electrical stimulation of the GSN and the IHN, we observed many combinations of somatic and visceral responses. We suggest that visceral afferent activity, in addition to being processed via convergent somatovisceral pathways, may be processed by neurons that convey only visceral information or by neurons in which visceral and somatic information is differentially coded.


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