Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats

2000 ◽  
Vol 279 (5) ◽  
pp. R1753-R1762 ◽  
Author(s):  
Ann M. Schreihofer ◽  
Patrice G. Guyenet
Keyword(s):  
Extracellular Recording ◽  
Splanchnic Nerve ◽  
Cell Types ◽  
Ventrolateral Medulla ◽  
Thoracic Spinal Cord ◽  
Catecholaminergic Neurons ◽  
Thoracic Spinal ◽  
Multiple Cell ◽  
Rvlm Neuron

The rostral ventrolateral medulla (RVLM) may play an important role in the sympatholytic and hypotensive effects of clonidine. The present study examined which type of presympathetic RVLM neuron is inhibited by clonidine, and whether the adrenergic presympathetic RVLM neurons are essential for clonidine-induced sympathoinhibition. In chloralose-anesthetized and ventilated rats, clonidine (10 μg/kg iv) decreased arterial pressure (116 ± 6 to 84 ± 2 mmHg) and splanchnic nerve activity (93 ± 3% from baseline). Extracellular recording and juxtacellular labeling of barosensitive bulbospinal RVLM neurons revealed that most cells were inhibited by clonidine (26/28) regardless of phenotype [tyrosine hydroxylase (TH)-immunoreactive cells: 48 ± 7%; non-TH-immunoreactive cells: 42 ± 5%], although the inhibition of most neurons was modest compared with the observed sympathoinhibition. Depletion of most bulbospinal catecholaminergic neurons, including 76 ± 5% of the rostral C1 cells, by microinjection of saporin anti-dopamine β-hydroxylase into the thoracic spinal cord (levels T2 and T4, 42 ng · 200 nl−1 · side−1) did not alter the sympatholytic or hypotensive effects of clonidine. These data show that although clonidine inhibits presympathetic C1 neurons, bulbospinal catecholaminergic neurons do not appear to be essential for the sympatholytic and hypotensive effects of systemically administered clonidine. Instead, the sympatholytic effect of clonidine is likely the result of a combination of effects on multiple cell types both within and outside the RVLM.

Sympathetic reflexes after depletion of bulbospinal catecholaminergic neurons with anti-DβH-saporin

2000 ◽  
Vol 279 (2) ◽  
pp. R729-R742 ◽  
Author(s):  
Ann M. Schreihofer ◽  
Patrice G. Guyenet
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Splanchnic Nerve ◽  
Ventrolateral Medulla ◽  
Thoracic Spinal Cord ◽  
Catecholaminergic Neurons ◽  
Thoracic Spinal ◽  
Sympathetic Reflexes ◽  
Spinal Injections

We examined the effects of destroying bulbospinal catecholaminergic neurons with the immunotoxin anti-dopamine β-hydroxylase-saporin (anti-DβH-Sap) on splanchnic nerve activity (SNA) and selected sympathetic reflexes in rats. Anti-DβH-Sap was administered into the thoracic spinal cord with the retrograde tracer fast blue. After 3–5 wk, anti-DβH-Sap eliminated most bulbospinal C1 (>74%), C3 (∼84%), A5 (∼98%), and A6 cells. Noncatecholaminergic bulbospinal neurons of the rostral ventrolateral medulla and serotonergic neurons were spared. Under chloralose anesthesia, mean arterial pressure and heart rate of anti-DβH-Sap-treated rats (3–5 wk) were normal. Resting SNA was not detectably altered, but the baroreflex range and gain were reduced ∼40% ( P < 0.05). Phenyl biguanide-induced decreases in mean arterial pressure, heart rate, and SNA were unchanged by anti-DβH-Sap, but the sympathoexcitatory response to intravenous cyanide was virtually abolished ( P < 0.05). Rats that received spinal injections of saporin conjugated to an anti-mouse IgG had intact bulbospinal C1 and A5 cells and normal physiological responses. These data suggest that C1 and A5 neurons contribute modestly to resting SNA and cardiopulmonary reflexes. However, bulbospinal catecholaminergic neurons appear to play a prominent sympathoexcitatory role during stimulation of chemoreceptors.

PNMT-containing neurons of the C1 cell group express c-fos in response to changes in baroreceptor input

1994 ◽  
Vol 266 (2) ◽  
pp. R361-R367 ◽  
Author(s):  
A. F. Sved ◽  
D. L. Mancini ◽  
J. C. Graham ◽  
A. M. Schreihofer ◽  
G. E. Hoffman
Keyword(s):  
Afferent Input ◽  
Protein Product ◽  
Early Gene ◽  
Ventrolateral Medulla ◽  
Cell Group ◽  
Afferent Activity ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Upper Thoracic

The immunocytochemical detection of Fos, the protein product of the immediate-early gene c-fos, was used as a marker for activated neurons to examine whether the C1 neurons in the rat rostral ventrolateral medulla (RVLM) respond to changes in baroreceptor afferent activity. After hydralazine-induced hypotension or sinoaortic denervation, two treatments that reduce baroreceptor afferent activity, numerous Fos-positive neurons were observed in the RVLM. The number of Fos-positive neurons in the RVLM was counted in brain stem sections from hydralazine-treated rats that had been previously injected with Fluorogold into the upper thoracic spinal cord to label spinally projecting RVLM neurons as well as stained for phenylethanolamine-N-methyltransferase (PNMT) as a marker of C1 neurons. The results indicate that approximately 80% of the C1 neurons expressed Fos in response to hydralazine injection; this was true of spinally projecting C1 neurons as well as those C1 neurons that were not labeled with Fluorogold. Furthermore, in hydralazine-treated rats, the majority of Fluorogold-labeled Fos-positive neurons contained PNMT. These results suggest that C1 neurons are sensitive to baroreceptor afferent input and support a role of these neurons in cardiovascular regulation.

scholarly journals Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

2016 ◽  
Vol 113 (34) ◽  
pp. E4995-E5004 ◽  
Author(s):  
Wen Lu ◽  
Michael Winding ◽  
Margot Lakonishok ◽  
Jill Wildonger ◽  
Vladimir I. Gelfand
Keyword(s):  
Cytoplasmic Streaming ◽  
Cell Types ◽  
Nurse Cells ◽  
Wild Type ◽  
Actin Cortex ◽  
Microtubule Motor ◽  
Multiple Cell ◽  
Cytoplasmic Microtubules ◽  
Two Populations

Cytoplasmic streaming in Drosophila oocytes is a microtubule-based bulk cytoplasmic movement. Streaming efficiently circulates and localizes mRNAs and proteins deposited by the nurse cells across the oocyte. This movement is driven by kinesin-1, a major microtubule motor. Recently, we have shown that kinesin-1 heavy chain (KHC) can transport one microtubule on another microtubule, thus driving microtubule–microtubule sliding in multiple cell types. To study the role of microtubule sliding in oocyte cytoplasmic streaming, we used a Khc mutant that is deficient in microtubule sliding but able to transport a majority of cargoes. We demonstrated that streaming is reduced by genomic replacement of wild-type Khc with this sliding-deficient mutant. Streaming can be fully rescued by wild-type KHC and partially rescued by a chimeric motor that cannot move organelles but is active in microtubule sliding. Consistent with these data, we identified two populations of microtubules in fast-streaming oocytes: a network of stable microtubules anchored to the actin cortex and free cytoplasmic microtubules that moved in the ooplasm. We further demonstrated that the reduced streaming in sliding-deficient oocytes resulted in posterior determination defects. Together, we propose that kinesin-1 slides free cytoplasmic microtubules against cortically immobilized microtubules, generating forces that contribute to cytoplasmic streaming and are essential for the refinement of posterior determinants.

Spinal NMDA receptors mediate pressor responses evoked from the rostral ventrolateral medulla

1991 ◽  
Vol 260 (1) ◽  
pp. H267-H275 ◽  
Author(s):  
M. K. Bazil ◽  
F. J. Gordon
Keyword(s):  
Spinal Cord ◽  
Heart Rate ◽  
Nmda Receptors ◽  
Excitatory Amino Acid ◽  
Cardiovascular Responses ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Pressor Responses

These studies investigated the role of spinal N-methyl-D-aspartic acid (NMDA) receptors in the mediation of cardiovascular responses evoked by L-glutamate (L-Glu) stimulation of the rostral ventrolateral medulla (RVM). Microinjections of L-Glu into the RVM of urethan-anesthetized rats increased mean arterial pressure (MAP) and heart rate. Intrathecal administration of the NMDA receptor antagonists D-(-)-2-amino-7-phosphonoheptanoic acid (D-AP-7) or 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) reduced MAP and heart rate. Blockade of NMDA receptors by D-AP-7 or CPP in the caudal thoracic spinal cord markedly reduced RVM pressor responses with little effect on evoked tachycardia. Administration of D-AP-7 to the rostral thoracic spinal cord had no effect on RVM pressor or tachycardic responses. Intrathecal D-AP-7 and CPP abolished the cardiovascular effects of intrathecal NMDA without reducing those produced by intrathecal kainic acid or the quisqualate agonist DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). These results indicate that 1) tonic activation of spinal NMDA receptors participates in the maintenance of sympathetic outflow to the heart and blood vessels, 2) pressor responses evoked from the RVM require synaptic activation of spinal NMDA receptors, and 3) an excitatory amino acid may be the neurotransmitter of pressor pathways descending from the RVM to the spinal cord.

scholarly journals Generation of a Quantitative Luciferase Reporter for Sox9 SUMOylation

2020 ◽  
Vol 21 (4) ◽  
pp. 1274
Author(s):  
Hideka Saotome ◽  
Atsumi Ito ◽  
Atsushi Kubo ◽  
Masafumi Inui
Keyword(s):  
Cell Types ◽  
Live Cells ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Post Translational Modifications ◽  
Extracellular Signal ◽  
Multiple Cell ◽  
Sox9 Activity ◽  
Reporter Signal

Sox9 is a master transcription factor for chondrogenesis, which is essential for chondrocyte proliferation, differentiation, and maintenance. Sox9 activity is regulated by multiple layers, including post-translational modifications, such as SUMOylation. A detection method for visualizing the SUMOylation in live cells is required to fully understand the role of Sox9 SUMOylation. In this study, we generated a quantitative reporter for Sox9 SUMOylation that is based on the NanoBiT system. The simultaneous expression of Sox9 and SUMO1 constructs that are conjugated with NanoBiT fragments in HEK293T cells induced luciferase activity in SUMOylation target residue of Sox9-dependent manner. Furthermore, the reporter signal could be detected from both cell lysates and live cells. The signal level of our reporter responded to the co-expression of SUMOylation or deSUMOylation enzymes by several fold, showing dynamic potency of the reporter. The reporter was active in multiple cell types, including ATDC5 cells, which have chondrogenic potential. Finally, using this reporter, we revealed a extracellular signal conditions that can increase the amount of SUMOylated Sox9. In summary, we generated a novel reporter that was capable of quantitatively visualizing the Sox9-SUMOylation level in live cells. This reporter will be useful for understanding the dynamism of Sox9 regulation during chondrogenesis.

scholarly journals Nitric Oxide Transiently Converts Synaptic Inhibition to Excitation in Retinal Amacrine Cells

2006 ◽  
Vol 95 (5) ◽  
pp. 2866-2877 ◽  
Author(s):  
Brian Hoffpauir ◽  
Emily McMains ◽  
Evanna Gleason
Keyword(s):  
Nitric Oxide ◽  
Hippocampal Neurons ◽  
Reversal Potential ◽  
Amacrine Cells ◽  
Cell Types ◽  
Synaptic Function ◽  
Positive Shift ◽  
Gabaergic Synapses ◽  
Multiple Cell

Nitric oxide (NO) is generated by multiple cell types in the vertebrate retina, including amacrine cells. We investigate the role of NO in the modulation of synaptic function using a culture system containing identified retinal amacrine cells. We find that moderate concentrations of NO alter GABAA receptor function to produce an enhancement of the GABA-gated current. Higher concentrations of NO also enhance GABA-gated currents, but this enhancement is primarily due to a substantial positive shift in the reversal potential of the current. Several pieces of evidence, including a similar effect on glycine-gated currents, indicate that the positive shift is due to an increase in cytosolic Cl−. This change in the chloride distribution is especially significant because it can invert the sign of GABA- and glycine-gated voltage responses. Furthermore, current- and voltage-clamp recordings from synaptic pairs of GABAergic amacrine cells demonstrate that NO transiently converts signaling at GABAergic synapses from inhibition to excitation. Persistence of the NO-induced shift in ECl− in the absence of extracellular Cl− indicates that the increase in cytosolic Cl− is due to release of Cl− from an internal store. An NO-dependent release of Cl− from an internal store is also demonstrated for rat hippocampal neurons indicating that this mechanism is not restricted to the avian retina. Thus signaling in the CNS can be fundamentally altered by an NO-dependent mobilization of an internal Cl− store.

Subgroups of Rostral Ventrolateral Medullary and Caudal Medullary Raphe Neurons Based on Patterns of Relationship to Sympathetic Nerve Discharge and Axonal Projections

1997 ◽  
Vol 77 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Susan M. Barman ◽  
Gerard L. Gebber
Keyword(s):  
Spinal Cord ◽  
Sympathetic Nerve ◽  
Cell Types ◽  
Vagus Nerves ◽  
Thoracic Spinal Cord ◽  
Axonal Projections ◽  
Thoracic Spinal ◽  
Medullary Raphe ◽  
Raphe Neurons ◽  
Nerve Discharge

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.

scholarly journals Role of expansile duraplasty and neural monitoring in surgery for Anterior Thoracic Spinal Cord Herniation

2020 ◽  
Vol 22 ◽  
pp. 100859
Author(s):  
Venugopal Sarath Chander ◽  
Ramachandran Govindasamy ◽  
Dheeraj Masapu ◽  
Veeramani Preethish-Kumar ◽  
Satish Rudrappa
Keyword(s):  
Spinal Cord ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Spinal Cord Herniation ◽  
Neural Monitoring

scholarly journals Collateralization of projections from the rostral ventrolateral medulla to the rostral and caudal thoracic spinal cord in felines

2012 ◽  
Vol 220 (2) ◽  
pp. 121-133 ◽  
Author(s):  
Michael F. Gowen ◽  
Sarah W. Ogburn ◽  
Takeshi Suzuki ◽  
Yoichiro Sugiyama ◽  
Lucy A. Cotter ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal

Bulbar catecholaminergic neurons projecting to the thoracic spinal cord of the chicken

1983 ◽  
Vol 167 (3) ◽  
pp. 411-423 ◽  
Author(s):  
Hirotaka Chikazawa ◽  
Toshitake Fujioka ◽  
Tohru Watanabe
Keyword(s):  
Spinal Cord ◽  
Thoracic Spinal Cord ◽  
Catecholaminergic Neurons ◽  
Thoracic Spinal
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