Retrotrapezoid nucleus chemoreception: mechanisms of function and contributions to disordered breathing in disease

Abstract

The brain regulates breathing in response to changes in CO₂/H⁺ by a process referred to as respiratory chemoreception. The retrotrapezoid nucleus (RTN) is essential for this function. RTN neurons are intrinsically activated by CO₂/H⁺. Astrocytes contribute as well, by providing a CO₂/H⁺-dependent purinergic drive to augment neural activity directly and indirectly by causing vasoconstriction. Here, we summarize preclinical studies in rodents that identify: (i) mechanisms of CO₂/H⁺ detection by RTN neurons; (ii) how this information is integrated at the neural network level; and (iii) how RTN neural activity is shaped by CO₂/H⁺ sensitive astrocytes. We also discuss how disruption of RTN chemoreception might contribute to breathing problems in disease, and highlight the therapeutic potential of targeting CO₂/H⁺-dependent and -independent regulatory elements of RTN neurons.

Keywords: apnea; astrocyte; hypercapnia; periodic breathing; respiration; vascular CO2/H(+) reactivity.