Acute exercise-induced activation of Phox2b-expressing neurons of the retrotrapezoid nucleus in rats may involve the hypothalamus

•Exercise evokes cardiorespiratory changes to facilitate CO2 removal and O2 uptake.•Chemosensitive RTN neurons are activated by running exercise.•RTN chemosensitive neurons may be implicated in the central command of exercise hyperpnea.

The rat retrotrapezoid nucleus (RTN) contains neurons that have a well-defined phenotype characterized by the presence of vesicular glutamate transporter 2 (VGLUT2) mRNA and a paired-like homeobox 2b (Phox2b)-immunoreactive (ir) nucleus and the absence of tyrosine hydroxylase (TH). These neurons are important to chemoreception. In the present study, we tested the hypothesis that the chemically-coded RTN neurons (ccRTN) (Phox2b+/TH−) are activated during an acute episode of running exercise. Since most RTN neurons are excited by the activation of perifornical and lateral hypothalamus (PeF/LH), a region that regulates breathing during exercise, we also tested the hypothesis that PeF/LH projections to RTN neurons contribute to their activation during acute exercise. In adult male Wistar rats that underwent an acute episode of treadmill exercise, there was a significant increase in c-Fos immunoreactive (c-Fos-ir) in PeF/LH neurons and RTN neurons that were Phox2b+TH− (p < 0.05) compared to rats that did not exercise. Also the retrograde tracer Fluoro-Gold that was injected into RTN was detected in c-Fos-ir PeF/LH (p < 0.05). In summary, the ccRTN neurons (Phox2b+TH−) are excited by running exercise. Thus, ccRTN neurons may contribute to both the chemical drive to breath and the feed-forward control of breathing associated with exercise.