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Defective respiratory rhythmogenesis and loss of central chemosensitivity in Phox2b mutants targeting retrotrapezoid nucleus neurons

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Item Type:Article
Title:Defective respiratory rhythmogenesis and loss of central chemosensitivity in Phox2b mutants targeting retrotrapezoid nucleus neurons
Creators Name:Dubreuil, V. and Thoby-Brisson, M. and Rallu, M. and Persson, K. and Pattyn, A. and Birchmeier, C. and Brunet, J.F. and Fortin, G. and Goridis, C.
Abstract:The retrotrapezoid nucleus (RTN) is a group of neurons in the rostral medulla, defined here as Phox2b-, Vglut2-, neurokinin1 receptor-, and Atoh1-expressing cells in the parafacial region, which have been proposed to function both as generators of respiratory rhythm and as central respiratory chemoreceptors. The present study was undertaken to assess these two putative functions using genetic tools. We generated two conditional Phox2b mutations, which target different subsets of Phox2b-expressing cells, but have in common a massive depletion of RTN neurons. In both conditional mutants as well as in the previously described Phox2b(27Ala) mutants, in which the RTN is also compromised, the respiratory-like rhythmic activity normally seen in the parafacial region of fetal brainstem preparations was completely abrogated. Rhythmic motor bursts were recorded from the phrenic nerve roots in the mutants, but their frequency was markedly reduced. Both the rhythmic activity in the RTN region and the phrenic nerve discharges responded to a low pH challenge in control, but not in the mutant embryos. Together, our results provide genetic evidence for the essential role of the Phox2b-expressing RTN neurons both in establishing a normal respiratory rhythm before birth and in providing chemosensory drive.
Keywords:Action Potentials, Chemoreceptor Cells, Homeodomain Proteins, Mutation, Nerve Net, Organ Culture Techniques, Phrenic Nerve, Respiration, Respiratory Center, Rhombencephalon, Transcription Factors, Animals, Mice
Source:Journal of Neuroscience
ISSN:0270-6474
Publisher:Society for Neuroscience (U.S.A.)
Volume:29
Number:47
Page Range:14836-14846
Date:25 November 2009
Official Publication:https://doi.org/10.1523/JNEUROSCI.2623-09.2009
PubMed:View item in PubMed

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