PT - JOURNAL ARTICLE AU - Sheng Wang AU - Yingtang Shi AU - Shaofang Shu AU - Patrice G. Guyenet AU - Douglas A. Bayliss TI - Phox2b-Expressing Retrotrapezoid Neurons Are Intrinsically Responsive to H<sup>+</sup> and CO<sub>2</sub> AID - 10.1523/JNEUROSCI.5550-12.2013 DP - 2013 May 01 TA - The Journal of Neuroscience PG - 7756--7761 VI - 33 IP - 18 4099 - http://www.jneurosci.org/content/33/18/7756.short 4100 - http://www.jneurosci.org/content/33/18/7756.full SO - J. Neurosci.2013 May 01; 33 AB - Central respiratory chemoreceptors sense changes in CO2/H+ and initiate the adjustments to ventilation required to preserve brain and tissue pH. The cellular nature of the sensors (neurons and/or glia) and their CNS location are not conclusively established but the glutamatergic, Phox2b-expressing neurons located in the retrotrapezoid nucleus (RTN) are strong candidates. However, a direct demonstration that RTN neurons are intrinsically sensitive to CO2/H+, required for designation as a chemosensor, has been lacking. To address this, we tested the pH sensitivity of RTN neurons that were acutely dissociated from two lines of Phox2b-GFP BAC transgenic mice. All GFP-labeled cells assayed by reverse transcriptase-PCR (n = 40) were Phox2b+, VGlut2+, TH−, and ChAT−, the neurochemical phenotype previously defined for chemosensitive RTN neurons in vivo. We found that most dissociated RTN neurons from both lines of mice were CO2/H+-sensitive (∼79%), with discharge increasing during acidification and decreasing during alkalization. The pH-sensitive cells could be grouped into two populations characterized by similar pH sensitivity but different basal firing rates, as previously observed in recordings from GFP-labeled RTN neurons in slice preparations. In conclusion, these data indicate that RTN neurons are inherently pH-sensitive, as expected for a respiratory chemoreceptor.