'Overlapping Mechanisms of Sleep and Sedation'

How general anaesthetics produce reversible loss of consciousness remains a mystery. The apparent lack of specificity, plus the observation that potency correlates with solubility in fat-like solvents, caused early workers to suppose that anaesthetics act directly on lipids. However, it is now accepted that general anaesthetics produce their effects at surgical levels by binding directly to a small number of protein targets, which have been identified for most general anaesthetics. Attention is now turning towards the possibility that the selectivity shown at the molecular level may extend to the level of neuronal networks, with some pathways being much more sensitive and important than others. Putting a patient to sleep with general anaesthetics has been used as a metaphor ever since their first clinical use, and as the mechanisms underlying natural sleep become better understood, the similarities between natural sleep and anaesthetic mechanisms have become more evident. The transitions between waking and sleeping and between the conscious and anaesthetised states may involve overlapping neuronal networks. I will describe recent work showing that overlapping ensembles of neurons in the pre-optic hypothalamus are involved in both deep sleep and drug-induced sedation, and that the same networks may be responsible for the hypothermia seen in both states.