QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 6, 2009, 29(18):5806-5819; doi:10.1523/JNEUROSCI.1106-09.2009

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Abbott, S. B. G. Articles by Guyenet, P. G. Search for Related Content PubMed PubMed Citation Articles by Abbott, S. B. G. Articles by Guyenet, P. G.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Photostimulation of Retrotrapezoid Nucleus Phox2b-Expressing Neurons In Vivo Produces Long-Lasting Activation of Breathing in Rats

Stephen B. G. Abbott,^1,2 * Ruth L. Stornetta,^1 * Michal G. Fortuna,¹ Seth D. Depuy,¹ Gavin H. West,¹ Thurl E. Harris,¹ and Patrice G. Guyenet¹

¹Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, and ²Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales 2109, Australia

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

The retrotrapezoid "nucleus" (RTN), located in the rostral ventrolateral medullary reticular formation, contains a bilateral cluster of 1000 glutamatergic noncatecholaminergic Phox2b-expressing propriobulbar neurons that are activated by CO₂ in vivo and by acidification in vitro. These cells are thought to function as central respiratory chemoreceptors, but this theory still lacks a crucial piece of evidence, namely that stimulating these particular neurons selectively in vivo increases breathing. The present study performed in anesthetized rats seeks to test whether this expectation is correct. We injected into the left RTN a lentivirus that expresses the light-activated cationic channel ChR2 (channelrhodopsin-2) (H134R mutation; fused to the fluorescent protein mCherry) under the control of the Phox2-responsive promoter PRSx8. Transgene expression was restricted to 423 ± 38 Phox2b-expressing neurons per rat consisting of noncatecholaminergic and C1 adrenergic neurons (3:2 ratio). Photostimulation delivered to the RTN region in vivo via a fiberoptic activated the CO₂-sensitive neurons vigorously, produced a long-lasting (t_1/2 = 11 s) increase in phrenic nerve activity, and caused a small and short-lasting cardiovascular stimulation. Selective lesions of the C1 cells eliminated the cardiovascular response but left the respiratory stimulation intact. In rats with C1 cell lesions, the mCherry-labeled axon terminals originating from the transfected noncatecholaminergic neurons were present exclusively in the lower brainstem regions that contain the respiratory pattern generator. These results provide strong evidence that the Phox2b-expressing noncatecholaminergic neurons of the RTN region function as central respiratory chemoreceptors.

---

Received March 6, 2009; revised March 31, 2009; accepted April 2, 2009.

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

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]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help