 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, October 4, 2006, 26(40):10305-10314; doi:10.1523/JNEUROSCI.2917-06.2006
Previous Article | Next Article
Neurobiology of Disease
Expression of Phox2b by Brainstem Neurons Involved in Chemosensory Integration in the Adult Rat
Ruth L. Stornetta,1 Thiago S. Moreira,1,2 Ana C. Takakura,1,2 Bong Jin Kang,3 Darryl A. Chang,1 Gavin H. West,1 Jean François Brunet,4 Daniel K. Mulkey,1 Douglas A. Bayliss,1 andPatrice G. Guyenet1 1Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, 2Department of Physiology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP 04023-060, Brazil, 3Department of Anesthesiology, Dankook University College of Medicine, Chonan City, Republic of Korea 330-715, and 4Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8542, Département de Biologie, Ecole Normale Supérieure, 75005 Paris, France
Correspondence should be addressed to Dr. Ruth Stornetta, University of Virginia Health System, P.O. Box 800735, 1300 Jefferson Park Avenue, Charlottesville, VA 22908-0735. Email: rs3j{at}virginia.edu
Central congenital hypoventilation syndrome is caused by mutations of the gene that encodes the transcription factor Phox2b. The syndrome is characterized by a severe form of sleep apnea attributed to greatly compromised central and peripheral chemoreflexes. In this study, we analyze whether Phox2b expression in the brainstem respiratory network is preferentially associated with neurons involved in chemosensory integration in rats. At the very rostral end of the ventral respiratory column (VRC), Phox2b was present in many VGlut2 (vesicular glutamate transporter 2) mRNA-containing neurons. These neurons were functionally identified as the respiratory chemoreceptors of the retrotrapezoid nucleus (RTN). More caudally in the VRC, many fewer neurons expressed Phox2b. These cells were not part of the central respiratory pattern generator (CPG), because they were typically cholinergic visceral motor neurons or catecholaminergic neurons (presumed C1 neurons). Phox2b was not detected in serotonergic neurons, in the A5, A6, and A7 noradrenergic cell groups nor within the main cardiorespiratory centers of the dorsolateral pons. Phox2b was expressed by many solitary tract nucleus (NTS) neurons including those that relay peripheral chemoreceptor information to the RTN. These and previous observations by others suggest that Phox2b is expressed by an uninterrupted chain of neurons involved in the integration of peripheral and central chemoreception (carotid bodies, chemoreceptor afferents, chemoresponsive NTS neurons projecting to VRC, RTN chemoreceptors). The presence of Phox2b in this circuit and its apparent absence from the respiratory CPG could explain why Phox2b mutations disrupt breathing automaticity during sleep without causing major impairment of respiration during waking.
Key words: respiration; central congenital hypoventilation syndrome; retrotrapezoid nucleus; central chemoreceptors; medulla oblongata; pons; central autonomic pathways
Received July 10, 2006; revised Aug. 21, 2006; accepted Aug. 24, 2006.
Correspondence should be addressed to Dr. Ruth Stornetta, University of Virginia Health System, P.O. Box 800735, 1300 Jefferson Park Avenue, Charlottesville, VA 22908-0735. Email: rs3j{at}virginia.edu
Related articles in J. Neurosci.:
- This Week in The Journal
J. Neurosci. 2006 26: i.[Full Text]
This article has been cited by other articles:
M. G. Fortuna, R. L. Stornetta, G. H. West, and P. G. Guyenet
Activation of the retrotrapezoid nucleus by posterior hypothalamic stimulation
J. Physiol., November 1, 2009; 587(21): 5121 - 5138.
[Abstract] [Full Text] [PDF]
V. Dubreuil, J. Barhanin, C. Goridis, and J.-F. Brunet
Breathing with Phox2b
Phil Trans R Soc B, September 12, 2009; 364(1529): 2477 - 2483.
[Abstract] [Full Text] [PDF]
J. S. Erlichman, A. C. Boyer, P. Reagan, R. W. Putnam, N. A. Ritucci, and J. C. Leiter
Chemosensory Responses to CO2 in Multiple Brain Stem Nuclei Determined Using a Voltage-Sensitive Dye in Brain Slices From Rats
J Neurophysiol, September 1, 2009; 102(3): 1577 - 1590.
[Abstract] [Full Text] [PDF]
S. B. G. Abbott, R. L. Stornetta, M. G. Fortuna, S. D. Depuy, G. H. West, T. E. Harris, and P. G. Guyenet
Photostimulation of Retrotrapezoid Nucleus Phox2b-Expressing Neurons In Vivo Produces Long-Lasting Activation of Breathing in Rats
J. Neurosci., May 6, 2009; 29(18): 5806 - 5819.
[Abstract] [Full Text] [PDF]
E. Nattie and A. Li
Central chemoreception is a complex system function that involves multiple brain stem sites
J Appl Physiol, April 1, 2009; 106(4): 1464 - 1466.
[Full Text] [PDF]
K. Amano, M. Fujii, S. Arata, T. Tojima, M. Ogawa, N. Morita, A. Shimohata, T. Furuichi, S. Itohara, H. Kamiguchi, et al.
DSCAM Deficiency Causes Loss of Pre-Inspiratory Neuron Synchroneity and Perinatal Death
J. Neurosci., March 4, 2009; 29(9): 2984 - 2996.
[Abstract] [Full Text] [PDF]
P. Lee, Y.-N. Su, C.-J. Yu, P.-C. Yang, and H.-D. Wu
PHOX2B Mutation-Confirmed Congenital Central Hypoventilation Syndrome in a Chinese Family: Presentation From Newborn to Adulthood
Chest, February 1, 2009; 135(2): 537 - 544.
[Abstract] [Full Text] [PDF]
H. Onimaru, K. Ikeda, and K. Kawakami
CO2-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat
J. Neurosci., November 26, 2008; 28(48): 12845 - 12850.
[Abstract] [Full Text] [PDF]
S. Pagliardini, J. Ren, P. A. Gray, C. VanDunk, M. Gross, M. Goulding, and J. J. Greer
Central Respiratory Rhythmogenesis Is Abnormal in Lbx1- Deficient Mice
J. Neurosci., October 22, 2008; 28(43): 11030 - 11041.
[Abstract] [Full Text] [PDF]
P. G. Guyenet
The 2008 Carl Ludwig Lecture: retrotrapezoid nucleus, CO2 homeostasis, and breathing automaticity
J Appl Physiol, August 1, 2008; 105(2): 404 - 416.
[Abstract] [Full Text] [PDF]
A. Khan, H. B. Sarnat, and R. Spaetgens
Congenital Muscle Fiber-Type Disproportion in a Patient With Congenital Central Hypoventilation Syndrome Due to PHOX2B Mutations
J Child Neurol, July 1, 2008; 23(7): 829 - 831.
[Abstract] [PDF]
M. B. Dias, A. Li, and E. Nattie
Focal CO2 dialysis in raphe obscurus does not stimulate ventilation but enhances the response to focal CO2 dialysis in the retrotrapezoid nucleus
J Appl Physiol, July 1, 2008; 105(1): 83 - 90.
[Abstract] [Full Text] [PDF]
A. C. Takakura, T. S. Moreira, R. L. Stornetta, G. H. West, J. M. Gwilt, and P. G. Guyenet
Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apnoeic threshold in rats
J. Physiol., June 15, 2008; 586(12): 2975 - 2991.
[Abstract] [Full Text] [PDF]
P. A. Gray
Transcription factors and the genetic organization of brain stem respiratory neurons
J Appl Physiol, May 1, 2008; 104(5): 1513 - 1521.
[Abstract] [Full Text] [PDF]
P. G. Guyenet, R. L. Stornetta, and D. A. Bayliss
Retrotrapezoid nucleus and central chemoreception
J. Physiol., April 15, 2008; 586(8): 2043 - 2048.
[Abstract] [Full Text] [PDF]
M. G. Fortuna, G. H. West, R. L. Stornetta, and P. G. Guyenet
Botzinger Expiratory-Augmenting Neurons and the Parafacial Respiratory Group
J. Neurosci., March 5, 2008; 28(10): 2506 - 2515.
[Abstract] [Full Text] [PDF]
V. Dubreuil, N. Ramanantsoa, D. Trochet, V. Vaubourg, J. Amiel, J. Gallego, J.-F. Brunet, and C. Goridis
A human mutation in Phox2b causes lack of CO2 chemosensitivity, fatal central apnea, and specific loss of parafacial neurons
PNAS, January 22, 2008; 105(3): 1067 - 1072.
[Abstract] [Full Text] [PDF]
D. K. Mulkey, E. M. Talley, R. L. Stornetta, A. R. Siegel, G. H. West, X. Chen, N. Sen, A. M. Mistry, P. G. Guyenet, and D. A. Bayliss
TASK Channels Determine pH Sensitivity in Select Respiratory Neurons But Do Not Contribute to Central Respiratory Chemosensitivity
J. Neurosci., December 19, 2007; 27(51): 14049 - 14058.
[Abstract] [Full Text] [PDF]
D. K. Mulkey, D. L. Rosin, G. West, A. C. Takakura, T. S. Moreira, D. A. Bayliss, and P. G. Guyenet
Serotonergic Neurons Activate Chemosensitive Retrotrapezoid Nucleus Neurons by a pH-Independent Mechanism
J. Neurosci., December 19, 2007; 27(51): 14128 - 14138.
[Abstract] [Full Text] [PDF]
T. S. Moreira, A. C. Takakura, E. Colombari, and P. G. Guyenet
Activation of 5-Hydroxytryptamine Type 3 Receptor-Expressing C-Fiber Vagal Afferents Inhibits Retrotrapezoid Nucleus Chemoreceptors in Rats
J Neurophysiol, December 1, 2007; 98(6): 3627 - 3637.
[Abstract] [Full Text] [PDF]
N. Ramanantsoa, V. Vaubourg, B. Matrot, G. Vardon, S. Dauger, and J. Gallego
Effects of temperature on ventilatory response to hypercapnia in newborn mice heterozygous for transcription factor Phox2b
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R2027 - R2035.
[Abstract] [Full Text] [PDF]
A. C. Takakura, T. S. Moreira, G. H. West, J. M. Gwilt, E. Colombari, R. L. Stornetta, and P. G. Guyenet
GABAergic Pump Cells of Solitary Tract Nucleus Innervate Retrotrapezoid Nucleus Chemoreceptors
J Neurophysiol, July 1, 2007; 98(1): 374 - 381.
[Abstract] [Full Text] [PDF]
E. E. Benarroch
Brainstem respiratory chemosensitivity: New insights and clinical implications
Neurology, June 12, 2007; 68(24): 2140 - 2143.
[Full Text] [PDF]
T. S. Moreira, A. C. Takakura, E. Colombari, G. H. West, and P. G. Guyenet
Inhibitory input from slowly adapting lung stretch receptors to retrotrapezoid nucleus chemoreceptors
J. Physiol., April 1, 2007; 580(1): 285 - 300.
[Abstract] [Full Text] [PDF]
E. E. Benarroch, A. M. Schmeichel, P. A. Low, and J. E. Parisi
Depletion of putative chemosensitive respiratory neurons in the ventral medullary surface in multiple system atrophy
Brain, February 1, 2007; 130(2): 469 - 475.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|