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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 586/12/2975    most recent jphysiol.2008.153163v2 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 Google Scholar Google Scholar Articles by Takakura, A. C. Articles by Guyenet, P. G. Search for Related Content PubMed PubMed Citation Articles by Takakura, A. C. Articles by Guyenet, P. G. Related Collections Respiratory

¹ Department of Physiology, UNIFESP-EPM, São Paulo, SP, 04023-060, Brazil
² Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA

Injection of the neurotoxin saporin–substance P (SSP-SAP) into the retrotrapezoid nucleus (RTN) attenuates the central chemoreflex in rats. Here we ask whether these deficits are caused by the destruction of a specific type of interneuron that expresses the transcription factor Phox2b and is non-catecholaminergic (Phox2b⁺TH^–). We show that RTN contains around 2100 Phox2b⁺TH^– cells. Injections of SSP-SAP into RTN destroyed Phox2b⁺TH^– neurons but spared facial motoneurons, catecholaminergic and serotonergic neurons and the ventral respiratory column caudal to the facial motor nucleus. Two weeks after SSP-SAP, the apnoeic threshold measured under anaesthesia was unchanged when fewer than 57% of the Phox2b⁺TH^– neurons were destroyed. However, destruction of 70 ± 3.5% of these cells was associated with a dramatic rise of the apnoeic threshold (from 5.6 to 7.9% end-expiratory P_CO²). In anaesthetized rats with unilateral lesions of around 70% of the Phox2b⁺TH^– neurons, acute inhibition of the contralateral intact RTN with muscimol instantly eliminated phrenic nerve discharge (PND) but normal PND could usually be elicited by strong peripheral chemoreceptor stimulation (8/12 rats). Muscimol had no effect in rats with an intact contralateral RTN. In conclusion, the destruction of the Phox2b⁺TH^– neurons is a plausible cause of the respiratory deficits caused by injection of SSP-SAP into RTN. Two weeks after toxin injection, 70% of these cells must be killed to cause a severe attenuation of the central chemoreflex under anaesthesia. The loss of an even greater percentage of these cells would presumably be required to produce significant breathing deficits in the awake state.

(Received 27 February 2008; accepted after revision 17 April 2008; first published online 25 April 2008)
Corresponding author P. G. Guyenet: University of Virginia Health System, PO Box 800735, 1300 Jefferson Park Avenue, Charlottesville, VA 22908-0735, USA. Email: pgg{at}virginia.edu

This paper has online supplemental material.

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