Selective innervation of upper and lower thoracic spinal segments by medullary raphe neurons in felines

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.

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Differential control of sympathetic nerve discharge by the brain stem

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1984.247.3.r513 ◽

1984 ◽

Vol 247 (3) ◽

pp. R513-R519 ◽

Cited By ~ 7

Author(s):

S. M. Barman ◽

G. L. Gebber ◽

F. R. Calaresu

Keyword(s):

Brain Stem ◽

Sympathetic Nerve ◽

Sympathetic Nerves ◽

Frequency Component ◽

External Carotid ◽

Medullary Raphe ◽

Reticular Neurons ◽

Differential Control ◽

The Brain ◽

Raphe Neurons

This investigation was designed to test the hypothesis that the brain stem differentially controls the basal discharges of postganglionic sympathetic nerves distributed to different organs. Previous studies have shown that the 2- to 6-Hz activity pattern in sympathetic nerves of the baroreceptor-denervated cat originates in the brain stem. In the current study, autocorrelation and power spectral analyses were used to compare the 2- to 6-Hz frequency components of the simultaneously recorded discharges of postganglionic sympathetic nerve pairs (inferior cardiac and renal; external carotid and renal) in baroreceptor-denervated cats anesthetized with sodium diallylbarbiturate and urethan (Dialurethane). In addition, spike-triggered averaging was used to compare the relative strengths of coupling of the basal discharges of single ventrolateral medullary reticular or medullary raphe neurons to activity in postganglionic sympathetic nerve pairs. The major findings of the study are as follows: 1) the predominant 2- to 6-Hz frequency component in the basal discharges of one sympathetic nerve often was different from that in the discharges of a second nerve, and 2) the activity of approximately one-third of ventrolateral medullary reticular neurons and one-half of medullary raphe neurons (with sympathetic-related activity) was differentially related to the discharges of postganglionic nerve pairs. These results support the view that the brain stem reticular formation and raphe complex exert their influences on different sympathetic nerves in a nonuniform fashion.

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Role of serotonergic neurons in the maintenance of the 10-Hz rhythm in sympathetic nerve discharge

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.270.1.r174 ◽

1996 ◽

Vol 270 (1) ◽

pp. R174-R181 ◽

Cited By ~ 6

Author(s):

H. S. Orer ◽

M. E. Clement ◽

S. M. Barman ◽

S. Zhong ◽

G. L. Gebber ◽

...

Keyword(s):

Sympathetic Nerve ◽

Peak Frequency ◽

Inhibitory Effects ◽

Receptor Agonists ◽

Naturally Occurring ◽

Medullary Raphe ◽

Receptor Agonists And Antagonists ◽

Raphe Neurons ◽

Nerve Discharge

We studied the effects of serotonin (5-HT)-receptor agonists and antagonists on the naturally occurring 10-Hz rhythm in sympathetic nerve discharge (SND) of urethan-anesthetized, baroreceptor-denervated cats. Intravenous doses of the 5-HT1A-receptor agonists 8-hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT) and U-93385E, which inhibit the firing of serotonergic medullary raphe neurons, decreased the power in the 10-Hz band of SND without affecting the power at frequencies < or = 6 Hz. The inhibitory effects of 8-OH-DPAT and U-93385E were reversed by the 5-HT1A-receptor antagonists spiperone and WAY-100135. Microinjection of 8-OH-DPAT into medullary raphe nuclei also selectively eliminated the 10-Hz rhythm in SND. Intravenous administration of the 5-HT2-receptor antagonist methysergide blocked the 10-Hz rhythm in SND, whereas the 5-HT2-receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane increased peak frequency and power in the 10-Hz band of SND. Microinjection of N-methyl-D-aspartic acid into the medullary raphe also enhanced the 10-Hz rhythm in SND. These data support the view that the naturally occurring discharges of serotonergic medullary raphe neurons preferentially enhance the 10-Hz rhythm in SND.

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Ligamentum flavum hematoma in the rigid thoracic spinal segments

Journal of Neurosurgery Spine ◽

10.3171/spi.2005.2.4.0495 ◽

2005 ◽

Vol 2 (4) ◽

pp. 495-497 ◽

Cited By ~ 8

Author(s):

Naohisa Miyakoshi ◽

Yoichi Shimada ◽

Kyoji Okada ◽

Michio Hongo ◽

Yuji Kasukawa ◽

...

Keyword(s):

Lumbar Spine ◽

Ligamentum Flavum ◽

Facet Joint ◽

Axial Stress ◽

Spinal Nerve ◽

Content Type ◽

First Case ◽

Thoracic Spinal ◽

Thoracolumbar Region ◽

Spinal Segments

✓ Ligamentum flavum hematoma, a rare cause of spinal nerve root and canal compression, typically occurs in the mobile lumbar spine segments. A thoracic ligamentum flavum hematoma is extremely rare—only one such case of a thoracolumbar (T11–12) lesion has been reported. The thoracolumbar region with its floating ribs, however, is structurally and biomechanically similar to the lumbar spine and its mobility is greater than the higher thoracic levels. To the best of their knowledge, the authors report the first case of a ligamentum flavum hematoma in the region of the rigid thoracic spinal segments with the contiguous rib cage. A symptomatic T9–10 ligamentum flavum hematoma is described in the case of a 66-year-old woman with compensatory thoracic lordosis secondary to the lumbar degenerative kyphosis. The hematoma was removed and the diagnosis was histologically confirmed. The authors speculate that thoracic lordosis might have contributed to the development of the hematoma because the ligamentum flavum and the facet joint were subjected to greater axial stress than in individuals with normal spinal alignment.

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Acidosis-Stimulated Neurons of the Medullary Raphe Are Serotonergic

Journal of Neurophysiology ◽

10.1152/jn.2001.85.5.2224 ◽

2001 ◽

Vol 85 (5) ◽

pp. 2224-2235 ◽

Cited By ~ 131

Author(s):

Wengang Wang ◽

Jyoti K. Tiwari ◽

Stefania Risso Bradley ◽

Rey V. Zaykin ◽

George B. Richerson

Keyword(s):

Cell Culture ◽

Substance P ◽

Tryptophan Hydroxylase ◽

Brain Slices ◽

Serotonergic Neurons ◽

Electrophysiological Properties ◽

Medullary Raphe ◽

Raphe Neurons

Neurons of the medullary raphe project widely to respiratory and autonomic nuclei and contain co-localized serotonin, thyrotropin-releasing hormone (TRH), and substance P, three neurotransmitters known to stimulate ventilation. Some medullary raphe neurons are highly sensitive to pH and CO2 and have been proposed to be central chemoreceptors. Here it was determined whether these chemosensitive neurons are serotonergic. Cells were microdissected from the rat medullary raphe and maintained in primary cell culture for 13–70 days. Immunoreactivity for serotonin, substance P, and TRH was present in these cultures. All acidosis-stimulated neurons ( n = 22) were immunoreactive for tryptophan hydroxylase (TpOH-IR), the rate-limiting enzyme for serotonin biosynthesis, whereas all acidosis-inhibited neurons ( n= 16) were TpOH-immunonegative. The majority of TpOH-IR medullary raphe neurons (73%) were stimulated by acidosis. The electrophysiological properties of TpOH-IR neurons in culture were similar to those previously reported for serotonergic neurons in vivo and in brain slices. These properties included wide action potentials (4.55 ± 0.5 ms) with a low variability of the interspike interval, a postspike afterhyperpolarization (AHP) that reversed 25 mV more positive than the Nernst potential for K+, prominent A current, spike frequency adaptation and a prolonged AHP after a depolarizing pulse. Thus the intrinsic cellular properties of serotonergic neurons were preserved in cell culture, indicating that the results obtained using this in vitro approach are relevant to serotonergic neurons in vivo. These results demonstrate that acidosis-stimulated neurons of the medullary raphe contain serotonin. We propose that serotonergic neurons initiate a homeostatic response to changes in blood CO2 that includes increased ventilation and modulation of autonomic function.

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Muscimol inhibition of medullary raphé neurons decreases the CO2 response and alters sleep in newborn piglets

Respiratory Physiology & Neurobiology ◽

10.1016/s1569-9048(02)00168-4 ◽

2002 ◽

Vol 133 (3) ◽

pp. 197-214 ◽

Cited By ~ 33

Author(s):

Michelle L Messier ◽

Aihua Li ◽

Eugene E Nattie

Keyword(s):

Co2 Response ◽

Newborn Piglets ◽

Medullary Raphe ◽

Raphe Neurons

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GABAergic neurons of the medullary raphe regulate active expiration during hypercapnia

Journal of Neurophysiology ◽

10.1152/jn.00698.2019 ◽

2020 ◽

Vol 123 (5) ◽

pp. 1933-1943 ◽

Cited By ~ 1

Author(s):

Josiane do N. Silva ◽

Luiz M. Oliveira ◽

Felipe C. Souza ◽

Thiago S. Moreira ◽

Ana C. Takakura

Keyword(s):

Gabaergic Neurons ◽

Medullary Raphe ◽

Raphe Neurons

Medullary raphe has been involved in the inspiratory response to central chemoreflex; however, these reports have never addressed the role of raphe neurons on active expiration induced by hypercapnia. Here, we showed that a subset of GABA cells within the medullary raphe directly project to the parafacial respiratory region, modulating active expiration under high levels of CO2.

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Interactive drives from two brain stem premotor nuclei are essential to support rat tail sympathetic activity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00005.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. R1107-R1115 ◽

Cited By ~ 37

Author(s):

Y. Ootsuka ◽

R. M. McAllen

Keyword(s):

Brain Stem ◽

Rectal Temperature ◽

Sympathetic Activity ◽

Chemical Stimulation ◽

Ventrolateral Medulla ◽

Sympathetic Fiber ◽

Medullary Raphe ◽

Cell Groups ◽

Raphe Neurons ◽

Stimulation Of

Anatomical studies indicate that sympathetic preganglionic neurons receive inputs from several brain stem cell groups, but the functional significance of this organization for vasomotor control is not known. We studied the roles of two brain stem premotor cell groups, the medullary raphé and the rostral ventrolateral medulla (RVLM), in determining the activity of sympathetic vasomotor supply to the tail of urethane-anesthetized, artificially ventilated rats. Chemical inactivation of either RVLM (bilaterally) or raphé cells by microinjecting glycine (120–200 nl, 0.5 M) or muscimol (40–160 nl, 2.1–8 mM) was sufficient to inhibit ongoing tail sympathetic fiber activity and to block its normally strong response to mild cooling via the trunk skin (reducing rectal temperature from 38.5 to 37°C). After bilateral RVLM inactivation, tail sympathetic fibers could still be excited by chemical stimulation of raphé neurons (l-glutamate, 120 nl, 50 mM), and strong cooling (rectal temperature ∼33°C) caused a low level of ongoing activity. After chemical inhibition of raphé neurons, however, neither strong cooling nor chemical stimulation of RVLM neurons activated tail sympathetic fibers. Electrical stimulation of the RVLM elicited tail sympathetic fiber volleys before and after local anesthesia of the raphé (150–500 nl of 5% tetracaine), demonstrating the existence of an independent descending excitatory pathway from the RVLM. The data show that neurons in both the medullary raphé and the RVLM, acting together, provide the essential drive to support vasomotor tone to the tail. Inputs from these two premotor nuclei interact in a mutually facilitatory manner to determine tonic, and cold-induced, tail sympathetic activity.

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Medullary serotonin neurons are CO2 sensitive in situ

Journal of Neurophysiology ◽

10.1152/jn.00288.2013 ◽

2013 ◽

Vol 110 (11) ◽

pp. 2536-2544 ◽

Cited By ~ 25

Author(s):

Kimberly E. Iceman ◽

George B. Richerson ◽

Michael B. Harris

Keyword(s):

Tryptophan Hydroxylase ◽

Extracellular Recording ◽

Central Chemosensitivity ◽

Central Chemoreceptors ◽

Medullary Raphe ◽

Serotonin Neurons ◽

Raphe Neurons

Brainstem central chemoreceptors are critical to the hypercapnic ventilatory response, but their location and identity are poorly understood. When studied in vitro, serotonin-synthesizing (5-HT) neurons within the rat medullary raphé are intrinsically stimulated by CO2/acidosis. The contributions of these neurons to central chemosensitivity in vivo, however, are controversial. Lacking is documentation of CO2-sensitive 5-HT neurons in intact experimental preparations and understanding of their spatial and proportional distribution. Here we test the hypothesis that 5-HT neurons in the rat medullary raphé are sensitive to arterial hypercapnia. We use extracellular recording and hypercapnic challenge of spontaneously active medullary raphé neurons in the unanesthetized in situ perfused decerebrate brainstem preparation to assess chemosensitivity of individual cells. Juxtacellular labeling of a subset of recorded neurons and subsequent immunohistochemistry for the 5-HT-synthesizing enzyme tryptophan hydroxylase (TPH) identify or exclude this neurotransmitter phenotype in electrophysiologically characterized chemosensitive and insensitive cells. We show that the medullary raphé houses a heterogeneous population, including chemosensitive and insensitive 5-HT neurons. Of 124 recorded cells, 16 cells were juxtacellularly filled, visualized, and immunohistochemically identified as 5-HT synthesizing, based on TPH-immunoreactivity. Forty-four percent of 5-HT cells were CO2 stimulated (increased firing rate with hypercapnia), while 56% were unstimulated. Our results demonstrate that medullary raphé neurons are heterogeneous and clearly include a subset of 5-HT neurons that are excited by arterial hypercapnia. Together with data identifying intrinsically CO2-sensitive 5-HT neurons in vitro, these results support a role for such cells as central chemoreceptors in the intact system.

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A rare case of thoracic spinal intradural extramedullary enterogenous cyst with acute onset: case report and literature review

Annals of The Royal College of Surgeons of England ◽

10.1308/rcsann.2019.0066 ◽

2019 ◽

Vol 101 (6) ◽

pp. e142-e146 ◽

Cited By ~ 1

Author(s):

CX Liu ◽

B Meng ◽

YB Li ◽

H Bai ◽

ZX Wu

Keyword(s):

Rare Case ◽

Acute Onset ◽

Neurenteric Cyst ◽

Enterogenous Cyst ◽

Diagnosis And Prognosis ◽

Thoracic Spinal ◽

Spinal Segments ◽

Intradural Extramedullary ◽

Radicular Symptoms ◽

Progressive Weakness

The intraspinal enterogenous cyst, also called an neurenteric cyst, is a rare congenital disease. It was reported to be local to the C1 to L2 spinal segments, with the majority located in the cervicothoracic region. Most patients present with symptoms of progressive focal pain, myelopathic signs or radicular symptoms. We report a rare case of thoracic spinal intradural extramedullary enterogenous cyst with rapidly progressive weakness of both lower extremities. Additionally, we analysed the literature concerning the clinical features, diagnosis and prognosis of this disease.

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