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Role of the retrotrapezoid nucleus phox2b-expressing neurons during mild-exercise in rats

      The level of activity of the rat retrotrapezoid nucleus (RTN) is regulated by converging inputs from wake-promoting systems, behavior-specific inputs from higher centers and by chemical drive. These neurons 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 the present study, we tested the hypothesis that RTN neurons could be activated by running mild exercise. Male Wistar rats (230–250 g, n=6) with a polyethylene cannula in the carotid artery were used. Rats were allocated to run in the treadmill (0.6 km/h) or remained sedentary for 30 min. After mild exercise, arterial PCO2 decreased (32±2, vs. sedentary 38±3%) and arterial PO2 increased (112±3, vs. sedentary 95±2%). No changes in lactate or pH were observed after exercise. Immunohistochemistry of brainstem sections to identify activation (c-Fos expression) of RTN neurons (Phox2b+TH) showed that sedentary rats evoked minimal Fos expression (3±2%). In contrast, a significant number of RTN neurons (24±3%, p<0.05) expressed Fos after mild running exercise. In summary, some 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.
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