The hypoxic respiratory response of the pre-Bötzinger complex

Since the discovery of the pre-Bötzinger Complex (preBötC) as a crucial region for generating the main respiratory rhythm, our understanding of its cellular and molecular aspects has rapidly increased within the last few decades. It is now apparent that preBötC is a highly flexible neuronal network that reconfigures state-dependently to produce the most appropriate respiratory output in response to various metabolic challenges, such as hypoxia. However, the responses of the preBötC to hypoxic conditions can be varied based on the intensity, pattern, and duration of the hypoxic challenge. This review discusses the preBötC response to hypoxic challenges at the cellular and network level. Particularly, the involvement of preBötC in the classical biphasic response of the respiratory network to acute hypoxia is illuminated. Furthermore, the article discusses the functional and structural changes of preBötC neurons following intermittent and sustained hypoxic challenges. Accumulating evidence shows that the preBötC neural circuits undergo substantial changes following hypoxia and contribute to several types of the respiratory system's hypoxic ventilatory responses.