Chapter 2 Modelling Sleep and General Anaesthesia J.W. Sleigh, L. Voss, M.L. Steyn-Ross, D.A. Steyn-Ross, and M.T. Wilson 2.1 Introduction There is active controversy concerning the ideas about the relationship between the states of natural sleep and general anaesthesia (Hudetz 2008; Lu et al. 2008; Zecharia et al. 2009). Because, by definition, general anaesthetic drugs act to di- minish the conscious state of the central nervous system—they are said to bias the central nervous system to enter natural sleep-like modes of operation (Franks 2008; Lancel 1999; Lin et al. 1989). This is manifest in the many similarities between the electroencephalogram (EEG) of natural sleep and the EEG when the patient is re- ceiving modest doses of general anaesthetic. Further evidence to support this idea is found in a number of studies in which a sedated state may be induced (or re- versed) by microinjection of various anaesthetic (and anti-anaesthetic) substances into some discrete areas of the brain-stem and midbrain which have been shown to be critical in the co-ordination of natural sleep-wake transitions (Hudetz et al. 2003; Nelson et al. 2002; Alkire et al. 2007, 2009; Sukhotinsky et al. 2007). These sub- cortical arousal structures facilitate wakefulness by providing ongoing depolarizing neuromodulatory input to the cortex. It is hard to imagine a more evolutionarily important behavior for an animal than the ability to achieve the state of wakeful- ness. Therefore, it is not surprising that there exist many overlapping brain-stem systems that can activate the cerebral cortex—acting via a number of different chemical substances such as glutamate, acetylcholine, amines, and orexin. Presum- ably this huge redundancy makes the animal relatively insensitive to natural neu- romodulator toxins. However, there is a problem. The sleep state seems, also, to be essential for the survival of animals with adaptive nervous systems. Therefore, J.W. Sleigh ( ) Department of Anaesthesia, Waikato Clinical School, University of Auckland, Hamilton, New Zealand e-mail: sleighj@waikatodhb.govt.nz A. Hutt (ed.), Sleep and Anesthesia, Springer Series in Computational Neuroscience 15, DOI 10.1007/978-1-4614-0173-5_2, © Springer Science+Business Media, LLC 2011 21