To breathe or not to breathe? That is the question

Our understanding of the role of the brain in respiratory rhythm generation and regulation began the early nineteenth century. Over the next 150 years the neuronal groups in the medulla oblongata and pons that were involved in eupnoea and in gasping were identified by techniques involving the lesioning of areas of the lower brainstem, several transections across the brainstem and focal electrical stimulation. An incomplete picture emerged that stressed the importance of the ventral medulla. Subsequent electrophysiological studies in in vivo, in situ and in vitro preparations have revealed the importance of restricted groups of neurones in this area, within the Bötzinger and pre-Bötzinger nuclei, that are the essential kernel for rhythm generation. The outputs to the spinal motoneurones responsible for the patterning of inspiratory and expiratory discharge are shaped by inputs from these neurones and others within the respiratory complex that determine the activity of respiratory bulbospinal neurones. It is clear that the developmental stage of the preparation is often critical for the pattern of respiratory activity that is generated and that these patterns have important physiological consequences. The models that are currently considered to explain rhythmogenesis are critically evaluated. The respiratory network is subject to regulation from peripheral and central chemoreceptors, amongst other afferent inputs, which act to ensure respiratory homeostasis. The roles of peripheral chemoreceptors as primarily O(2) sensors are considered, and the evolution of ideas surrounding their roles is described. New insights into the transduction mechanisms of chemoreception in the carotid body and chemosensitive areas of the ventral medullary surface, specifically in monitoring CO(2) levels, are reviewed. As new experimental tools, both genetic and cellular, are emerging, it can be expected that the detailed network architecture and synaptic interactions that pattern respiratory activity in relation to behavioural activity will be revealed over the next years.