Differences in respiratory changes and Fos expression in the ventrolateral medulla of rats exposed to hypoxia, hypercapnia, and hypercapnic hypoxia

• Respiratory frequency was increased in rats exposed to hypoxia.
• Fos-positive neurons were observed in the caudal and medial VLM in rats exposed to hypoxia.
• Tidal volume was increased in rats exposed to hypercapnia and hypercapnic hypoxia.
• Fos-positive neurons were observed in rostral and medial VLM in rats exposed to hypercapnia.
• Fos-positive neurons were observed in entire region of VLM in rats exposed to hypercapnic hypoxia.

Respiratory responses to hypoxia and/or hypercapnia, and their relationship to neural activity in the ventrolateral medulla (VLM), which includes the respiratory center, have not yet been elucidated in detail. We herein examined respiratory responses during exposure of 10% O2 (hypoxia), 10% CO2 (hypercapnia), and 10% O2–10% CO2 (hypercapnic hypoxia) using plethysmography. In addition to recording respiration, Fos expressions were examined in the VLM of the rat exposed to each gas to analyze neural activity. Respiratory frequency was increased in rats exposed to hypoxia, and Fos-positive neurons were observed in the caudal VLM (cVLM) and medial VLM (mVLM). Tidal volume was increased in rats exposed to hypercapnia, and Fos-positive neurons were observed in the rostral VLM (rVLM) includes the retrotrapezoid nucleus (RTN) and mVLM. Tidal volume was enhanced in rats exposed to hypercapnic hypoxia, similar to that in hypercapnia-exposed rats, and Fos-positive neurons were observed in the entire region of the VLM. In the mVLM and cVLM, double immunofluorescence showed Fos-immunoreactive nerve cells were also immunoreactive to dopamine β-hydroxylase, the marker for A1/C1 catecholaminergic neuron. These results suggested that hypoxia and hypercapnia modulated rhythmogenic microcircuits in the mVLM via A1/C1 neurons and the RTN, respectively.