State-dependent central chemoreception: A role of orexin

Sites involved in central chemoreception (CCR) are widely distributed in the brain. One possible explanation for the existence of multiple central chemoreceptor sites is the vigilance state-dependent hypothesis, that some sites are of greater importance in wakefulness others in sleep. We briefly summarize the evidence for a distributed network of central chemoreceptor sites and a vigilance state-dependent differentiation among them. We then discuss the role of orexin in vigilance state-dependent CCR based on our recent studies using orexin knockout mice and focal microdialysis of an orexin receptor antagonist at the retrotrapezoid nucleus and medullary raphe in rats. Orexin affects CCR in a vigilance state-dependent manner that varies with circadian time. Orexin also contributes to emotional stress- and other state-dependent related regulation of ventilation, e.g., the defense response. Diversity in central chemoreception including orexin neurons and the synaptic control of respiratory and cardiovascular output neurons appears to be necessary for animals to adapt themselves to constantly changing situations and behavioral states.