Multiple sites for central chemoreception: their roles in response sensitivity and in sleep and wakefulness

Central chemoreceptors appear to be widely distributed in the brainstem. Why are there so many central chemoreceptor sites? This review focuses on two hypotheses. (1) The high sensitivity of the respiratory control system as a whole to small changes in systemic P(CO(2)) results from an additive, or greater, effect of the multiple central chemoreceptor sites. Each site provides a fraction of the total response and, importantly, provides tonic excitatory input in eucapnia as well. (2) Individual central chemoreceptor sites vary in effectiveness depending on the arousal or vigilance state of the animal. For example, some sites are more important in wakefulness; others in sleep. Proof for these hypotheses depends critically on obtaining accurate measures of stimulus intensity at each chemoreceptor site in vivo.