Brainstem and hypothalamic areas involved in respiratory chemoreflexes: a Fos study in adult rats

The adaptation to hypoxia and hypercapnia requires the activation of several anatomical structures along the neuraxis. In this study, using Fos immunoreactivity, we sought to map neuronal populations involved in chemoreflex networks activated during the responses to moderate hypoxia (O(2) 11%), and hypercapnia (CO(2) 5%) in the brainstem and the hypothalamus of the rat. In the medulla, hypoxia elicited marked and significant staining in the nucleus of the solitary tract (NTS), and in parapyramidal neurons located near the ventral surface, whereas hypercapnia evoked significantly c-fos only near the ventral surface in paraolivar neurons. In contrast, within pontine and suprapontine structures, both hypoxia and hypercapnia evoked similarly Fos immunoreactivity in the lateral parabrachialis area, the central grey, the caudal hypothalamus (dorsomedial and posterior hypothalamic nuclei), and in a ventro-lateral hypothalamic area, extending from the rostral limit of the mammillary nuclei to the retrochiasmatic area. More rostrally, labelling was observed in the paraventricular nucleus of the hypothalamus in response to hypercapnia, and in the supraoptic nucleus in response to hypoxia. These results support the hypothesis that chemoreflexes pathways are not only restricted to medulla and pons but also involved mesencephalic and hypothalamic regions. The parabrachialis area and the central grey may be key relays between caudal and ventral hypothalamic neurons, and medullary neurons involved in the response to hypoxia and hypercapnia.