Multiple central chemoreceptor sites: cell types and function in vivo.

Central chemoreception is a distributed property involving many sites and neuronal types. Focal acidosis in conscious or anesthetized animals at many hindbrain sites stimulates breathing. The steady-state CO2 response in conscious animals is reduced by cell specific lesions of catecholamine, 5HT or neurokinin-1 receptor (NK1R) expressing neurons and by focal inhibition at the retrotrapezoid nucleus (RTN) and medullary raphe (MR). Is the steady-state CO2 response a physiologically relevant way to study central chemoreception? Central chemoreceptors also: (1) provide a 'tonic drive' to breathe, (2) are modified by and/or modulate other control systems, e.g., temperature and hypoxia, (3) affect breath-to-breath variability, (4) can respond dynamically to few breath changes in CO2, and (5) interact in complex ways. We contend that central chemoreceptors detect interstitial pH and thus monitor the balance of arterial PCO2, cerebral blood flow and neuronal/glial metabolism. They affect physiological control systems in many ways, perhaps not all measurable, via the study of the steady-state CO2 response.