It seems that whoever coined the expression 'life's a gas' was out by at least a factor of two. As a pair of reviews in this issue shows, we owe our lives to the brain's ability to detect and respond to fluctuating levels of both oxygen and carbon dioxide.

On page 437, Sharp and Bernaudin discuss the molecular and cellular mechanisms that mediate the brain's response to hypoxia. In particular, they highlight the pivotal role of the transcription factor hypoxia-inducible factor 1 (HIF1) in hypoxia sensing. At normal oxygen levels, the HIF1α subunit is rapidly degraded, but it accumulates in hypoxic cells and forms a dimer with HIFβ. This protein complex activates HIF1 target genes, which generate an adaptive response to low oxygen levels. The authors also consider the role of HIF1 in various neurological diseases, and show how it might be beneficial or harmful, depending on the circumstances.

As well as ensuring that the tissues of the body are adequately oxygenated, the brain also has a key role in maintaining carbon dioxide levels — and consequently tissue pH — within a narrow range. It has been known for some time that carbon dioxide-sensing neurons reside in the brainstem, but it was only recently that these cells were identified as serotonergic neurons. On page 449, Richerson discusses the role of the serotonergic system in pH homeostasis. He also considers some of the non-respiratory responses of the CNS to raised carbon dioxide levels, including anxiety and arousal from sleep. It has been suggested that serotonergic neuron dysfunction is one of the contributing factors to sudden infant death syndrome, so understanding the role of the serotonergic system in carbon dioxide sensing will be crucial for developing strategies to prevent this devastating condition.