Opposing effects of hypoxia on catecholaminergic locus coeruleus and hypocretin/orexin neurons in chick embryos

Terrestrial vertebrate embryos face a risk of low oxygen availability (hypoxia) that is especially great during their transition to air-breathing. To better understand how fetal brains respond to hypoxia, we examined the effects of low oxygen availability on brain activity in late-stage chick embryos (day 18 out of a 21-day incubation period). Using cFos protein expression as a marker for neuronal activity, we focused on two specific, immunohistochemically identified cell groups known to play an important role in regulating adult brain states (sleep and waking): the noradrenergic neurons of the Locus Coeruleus (NA-LC), and the Hypocretin/Orexin (H/O) neurons of the hypothalamus. cFos expression was also examined in the Pallium (the avian analog of the cerebral cortex). In adult mammalian brains, cFos expression changes in a coordinated way in these areas. In chick embryos, oxygen deprivation simultaneously activated NA-LC while deactivating H/O-producing neurons; it also increased cFos expression in the Pallium. Activity in one pallial primary sensory area was significantly related to NA-LC activity. These data reveal that at least some of the same neural systems involved in brain-state control in adults may play a central role in orchestrating prenatal hypoxic responses, and that these circuits may show different patterns of coordination than seen in adults.