Essential role of Phox2b-expressing ventrolateral brainstem neurons in the chemosensory control of inspiration and expiration

Nephtali Marina, Ana P Abdala, Stefan Trapp, Aihua Li, Eugene E Nattie, James Hewinson, Jeffrey C Smith, Julian F R Paton, Alexander V Gourine

Research output: Contribution to journalArticle (Academic Journal)peer-review

110 Citations (Scopus)

Abstract

Phox2b-expressing neurons of the retrotrapezoid nucleus (RTN), located in the ventrolateral brainstem, are sensitive to changes in PCO(2)/pH, have excitatory projections to the central respiratory rhythm/pattern generator, and their activation enhances central respiratory drive. Using in vivo (conscious and anesthetized rats) and in situ (arterially perfused rat brainstem-spinal cord preparations) models, we evaluated the functional significance of this neuronal population for both resting respiratory activity and the CO(2)-evoked respiratory responses by reversibly inhibiting these neurons using the insect peptide allatostatin following transduction with a lentiviral construct to express the G-protein-coupled Drosophila allatostatin receptor. Selective inhibition of the Phox2b-expressing neurons in the ventrolateral brainstem, including the RTN, using allatostatin was without effect on resting respiratory activity in conscious rats, but decreased the amplitude of the phrenic nerve discharge in anesthetized rats and the in situ rat preparations. Postinspiratory activity was also reduced in situ. In the absence or presence of the peripheral chemoreceptor input, inhibiting the Phox2b-expressing neurons during hypercapnia abolished the CO(2)-evoked abdominal expiratory activity in anesthetized rats and in situ preparations. Inspiratory responses evoked by rising levels of CO(2) in the breathing air were also reduced in anesthetized rats with denervated carotid bodies and conscious rats with peripheral chemoreceptors intact (by 28% and 60%, respectively). These data indicate a crucial dependence of central expiratory drive upon Phox2b-expressing neurons of the ventrolateral brainstem and support the hypothesis that these neurons contribute in a significant manner to CO(2)-evoked increases of inspiratory activity.
Translated title of the contributionEssential role of Phox2b-expressing ventrolateral brainstem neurons in the chemosensory control of inspiration and expiration
Original languageEnglish
Pages (from-to)12466 - 12473
Number of pages8
JournalJournal of Neuroscience
Volume30
Issue number37
DOIs
Publication statusPublished - Sep 2010

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