Expression of Phox2b by brainstem neurons involved in chemosensory integration in the adult rat

Expression of Phox2b by brainstem neurons involved in chemosensory integration in the adult rat

Author Stornetta, Ruth L. Google Scholar
Moreira, Thiago S. Google Scholar
Takakura, Ana C. Google Scholar
Kang, Bong Jin Google Scholar
Chang, Darryl A. Google Scholar
West, Gavin H. Google Scholar
Brunet, Jean Francois Google Scholar
Mulkey, Daniel K. Google Scholar
Bayliss, Douglas A. Google Scholar
Guyenet, Patrice G. Google Scholar
Institution Univ Virginia
Universidade Federal de São Paulo (UNIFESP)
Ecole Normale Super
Dankook Univ
Abstract 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.
Keywords respiration
central congenital hypoventilation syndrome
retrotrapezoid nucleus
central chemoreceptors
medulla oblongata
pons
central autonomic pathways
Language English
Date 2006-10-04
Published in Journal of Neuroscience. Washington: Soc Neuroscience, v. 26, n. 40, p. 10305-10314, 2006.
ISSN 0270-6474 (Sherpa/Romeo, impact factor)
Publisher Soc Neuroscience
Extent 10305-10314
Origin http://dx.doi.org/10.1523/JNEUROSCI.2917-06.2006
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000241192700024
URI http://repositorio.unifesp.br/handle/11600/29205

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