Development of hypoxia-induced Fos expression in rat caudal hypothalamic neurons

The caudal hypothalamus is an important CNS site controlling cardiorespiratory integration during systemic hypoxia. Previous findings from this laboratory have identified caudal hypothalamic neurons of anesthetized rats that are stimulated during hypoxia. In addition, patch-clamp recordings in an in vitro brain slice preparation have revealed that there is an age-dependent response to hypoxia in caudal hypothalamic neurons. The present study utilized the expression of the transcription factor Fos as an indicator of neuronal depolarization to determine the hypoxic response of caudal hypothalamic neurons throughout postnatal development in conscious rats. Sprague-Dawley rats, aged three to 56 days, were placed in a normobaric chamber circulated with either 10% oxygen or room air for 3h. Following the hypoxic/normoxic exposure period, tissues from the caudal hypothalamus, periaqueductal gray, rostral ventrolateral medulla and nucleus tractus solitarius were processed immunocytochemically for the presence of the Fos protein. There was a significant increase in the density of neurons expressing Fos in the caudal hypothalamus of hypoxic compared to normoxic adult rats that was maintained in the absence of peripheral chemoreceptors. In contrast, no increase in the density of Fos-expressing caudal hypothalamic neurons was observed during hypoxia in rats less than 12 days old. Increases in Fos expression were also observed in an age-dependent manner in the periaqueductal gray, rostral ventrolateral medulla and nucleus tractus solitarius. These results show an increase in Fos expression in caudal hypothalamic neurons during hypoxia in conscious rats throughout development, supporting the earlier in vitro reports suggesting that these neurons are stimulated by hypoxia.