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

The caudal hypothalamus is an important CNS site controlling cardiorespirat ory integration during systemic hypoxia. Previous findings from this labora tory 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 util ized the expression of the transcription factor Fos as an indicator of neur onal depolarization to determine the hypoxic response of caudal hypothalami c neurons throughout postnatal development in conscious rats. Sprague-Dawle y rats, aged three to 56 days, were placed in a normobaric chamber circulat ed with either 10% oxygen or room air for 3 h. Following the hypoxic/normox ic exposure period, tissues from the caudal hypothalamus, periaqueductal gr ay, rostral ventrolateral medulla and nucleus tractus solitarius were proce ssed 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 maintaine d in the absence of peripheral chemoreceptors. In contrast, no increase in the density of Fos-expressing caudal hypothalamic neurons was observed duri ng hypoxia in rats less than 12 days old. Increases in Fos expression were also observed in an age-dependent manner in the periaqueductal gray, rostra l ventrolateral medulla and nucleus tractus solitarius. These results show an increase in Fos expression in caudal hypothalamic neu rons during hypoxia in conscious rats throughout development, supporting th e earlier in vitro reports suggesting that these neurons are stimulated by hypoxia. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reser ved.