Activation of retrotrapezoid nucleus phox2b‐expressing neurons during exercise in rats

The rat retrotrapezoid nucleus (RTN) contains neurons that have a well‐defined phenotype characterized by the presence of vesicular glutamate transporter 2 (VGLUT2) mRNA, a paired‐like homeobox 2b (Phox2b)‐immunoreactive (ir) nucleus and the absence of tyrosine hydroxylase (TH). In addition, most RTN neurons are excited by posterior hypothalamic stimulation, a region that regulates breathing during sleep, stress and exercise. In the present study, we tested the hypothesis that RTN neurons could be activated during running exercise. Male Wistar rats (230–250 g, n = 6) were allocated to daily training or remained sedentary for 5 days. Immunohistochemistry of brainstem sections to identify activation (c‐Fos expression) of RTN neurons (Phox2b+TH‐) showed that sedentary rats evoked minimal Fos expression (7 ± 2%). In contrast, most RTN neurons (54 ± 4%) expressed Fos after mild exercise running. In summary, most RTN neurons are excited by running exercise while retaining their normal response to CNS acidification. RTN neurons probably contribute both to the chemical drive of breathing and to the feed‐forward control of breathing associated with exercise. Financial support: FAPESP (06/60174‐9 to TSM)