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The Journal of Neuroscience, March 5, 2008, 28(10):2506-2515; doi:10.1523/JNEUROSCI.5595-07.2008

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Behavioral/Systems/Cognitive
Bötzinger Expiratory-Augmenting Neurons and the Parafacial Respiratory Group

Michal G. Fortuna, Gavin H. West, Ruth L. Stornetta, and Patrice G. Guyenet

Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908

Correspondence should be addressed to Dr. Patrice G. Guyenet, University of Virginia Health System, P.O. Box 800735, 1300 Jefferson Park Avenue, Charlottesville, VA 22908-0735. Email: pgg{at}virginia.edu

In neonatal rat brains in vitro, the rostral ventral respiratory column (rVRC) contains neurons that burst just before the phrenic nerve discharge (PND) and rebound after inspiration (pre-I neurons). These neurons, called parafacial respiratory group (pfRG), have been interpreted as a master inspiratory oscillator, an expiratory rhythm generator or simply as neonatal precursors of retrotrapezoid (RTN) chemoreceptor neurons. pfRG neurons have not been identified in adults, and their phenotype is unknown. Here, we confirm that the rVRC normally lacks pre-I neurons in adult anesthetized rats. However, we show that, during hypercapnic hypoxia, a population of rVRC expiratory-augmenting (E-AUG) neurons consistently develops a pre-I discharge. These cells reside in the Bötzinger region of the rVRC, they express glycine-transporter-2, and their axons arborize throughout the VRC. Hypoxia triggers an identical pre-I pattern in retroambigual expiratory bulbospinal neurons, but this pattern is not elicited in Bötzinger expiratory-decrementing neurons, Bötzinger inspiratory neurons, RTN neurons, and blood pressure-regulating neurons. In conclusion, under hypoxia in vivo, abdominal expiratory premotor neurons of adult rats develop a pre-I pattern reminiscent of that observed in neonate brainstems in vitro. In the rVRC of adult rats, pre-I cells include selected rhythmogenic neurons (glycinergic Bötzinger neurons) but not RTN chemoreceptors. We suggest that the pfRG may not be an independent rhythm generator but a heterogeneous collection of E-AUG neurons (glycinergic Bötzinger neurons, possibly facial motor and premotor neurons), the discharge of which becomes preinspiratory under specific experimental conditions resulting from, in part, a prolonged and intensified activity of postinspiratory neurons.

Key words: breathing; hypoxia; parafacial respiratory group; retrotrapezoid nucleus; central chemoreceptors; medulla oblongata


Received Sept. 20, 2007; revised Jan. 21, 2008; accepted Jan. 22, 2008.

Correspondence should be addressed to Dr. Patrice G. Guyenet, University of Virginia Health System, P.O. Box 800735, 1300 Jefferson Park Avenue, Charlottesville, VA 22908-0735. Email: pgg{at}virginia.edu




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D. B. Zoccal, A. E. Simms, L. G. H. Bonagamba, V. A. Braga, A. E. Pickering, J. F. R. Paton, and B. H. Machado
Increased sympathetic outflow in juvenile rats submitted to chronic intermittent hypoxia correlates with enhanced expiratory activity
J. Physiol., July 1, 2008; 586(13): 3253 - 3265.
[Abstract] [Full Text] [PDF]



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