General anaesthetics put millions of people to sleep each year, but no one fully understands how these drugs actually switch off consciousness in the brain. This matters because current anaesthetics are blunt tools. They produce the desired loss of awareness, but also dangerous side effects such as respiratory depression—a particular risk for older or already frail patients. The same brain pathways that control natural sleep are likely involved, yet the two fields of research have largely operated separately. This programme aims to connect them, using newly identified protein targets for anaesthetic drugs to trace the specific neuronal circuits responsible for their effects. If the researchers succeed, the practical payoff could be substantial. Better understanding of which pathways produce unconsciousness versus which suppress breathing could guide the development of safer anaesthetics with fewer side effects. It could also illuminate how natural sleep is regulated, offering new avenues for treating insomnia and other sleep disorders that are increasingly common in society. This is primarily fundamental neuroscience—a major intellectual puzzle about how the brain transitions between conscious and unconscious states. But as the tragic case of Michael Jackson’s death from propofol misuse illustrates, the stakes are not merely academic. Even in controlled hospital settings, imperfect anaesthetics cause real harm.
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Modern surgery would be impossible without general anaesthetics, yet the underlying mechanisms by which these chemicals produce unconsciousness and pain relief are only now being discovered. In parallel with these insights about anaesthetic action, neuroscientists have identified some of the mechanisms that control and regulate natural sleep and consciousness. The aim of our Programme of research is to bring these aspects together so as to better understand how general anaesthetics and sedative drugs act in the brain. We hope to build upon the great advances that have been made over recent years in identifying the protein targets for some of these drugs and use this specificity to guide us towards pinpointing the neuronal pathways important for their actions. The drugs currently used to anaesthetise and sedate patients are far from perfect, providing a mix of desirable (such as loss of consciousness) and undesirable (such as respiratory depression) effects. Different anaesthetics and sedative drugs act on different pathways. Working out which pathways are responsible may help us develop better drugs with fewer side-effects. The dangers of current anaesthetics, and the absence of effective remedies for insomnia, are sadly illustrated by the death of the singer Michael Jackson following the inappropriate administration of the general anaesthetic propofol. However, even in the controlled environment of a hospital, many patients suffer from undesirable side-effects caused by the anaesthetic and analgesic drugs used during perioperative care. Serious risks can be provoked in already compromised patients, a considerable concern in our ageing population. Our work on anaesthetic action tackles a major intellectual problem in basic neuroscience, and at the same time, researching anaesthetic mechanisms and natural sleep pathways, and how they are related, can be expected to provide important information that has practical applications. For example, our work should provide insights into how natural sleep pathways work, information that is likely to aid in the treatment of sleep disorders, which are increasingly common in society.
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