‘Why do we sleep?’ At a satellite symposium of the 6th FENS Forum, over 140 scientists gathered at the shores of Lac Léman to ponder the many different facets of this question. Amongst them were 18 invited speakers representing a wide range of scientific disciplines including clinical practice, pharmacology, neurophysiology and genetics (the program of the meeting can be viewed at http://www.unil.ch/fens2008sleep). The large variety of disciplines represented and the lively interactions sparked by the speaker’s presentations bear witness to the growing interest of the neuroscience community in all aspects of sleep research and sleep medicine. Their opinions are summarized here in a series of nine reviews constituting this Special Issue of EJN.
Despite their heterogeneous background, the participants soon discovered that they shared a common language when discussing the functions of sleep in terms of brain mechanisms. However, different perspectives emerged when they attempted to generate a definition of sleep. What exactly is sleep? Can one identify a ‘minimal sleep unit’, a minimal entity that represents the essence of sleep? Does sleep concern the entire organism, its nervous system, specific neuronal networks, or just individual synapses? Is it possible to define sleep without knowing its function? And, what are the mechanisms underlying sleep disorders? Even the questions ‘how unique is sleep as a state’ and ‘is sleep indispensable’ did not generate consensus. In other words, is sleep fundamentally different from wakefulness? Does sleep actively mediate specific functions that do not occur in other states? Is sleep causally related to learning and memory, and does it promote synaptic plasticity at the cellular level? Is sleep, therefore, indispensable for cognitive function? Does sleep provide a state in which recovery processes are more efficacious than during wakefulness?
All participants agreed that a comprehensive definition of sleep should encompass the functions of sleep. Such a view implies that neuronal indicators of sleep evoke effects that indicate the functions of sleep. To this end, geneticists have identified differential molecular markers of wakefulness and sleep and suggested mechanisms that render the brain vulnerable to sleep loss. Cellular physiologists have described the neurophysiological and biochemical properties of sleep-promoting neurons and identified specific characteristics that indicate that these neurons are essential for the occurrence of sleep as a brain state. System physiologists have investigated brain activity in animals and humans in order to unravel the roles of sleep in cognitive functions and developed strategies for enhancing the cognitive benefits of sleep. Finally, clinicians have analyzed sleep deficits in patients and determined their effects on brain function and cognitive performance. The integration of findings from all these levels is expected to provide insights into the contribution of sleep to overall performance and well-being. It will be a major challenge to close the gaps among the different disciplines and translate the rapidly accumulating knowledge into benefits for patients suffering from sleep-related disorders.
The reviews presented in this Special Issue reflect on the broad range of topics presented at the symposium and recapitulate the primary questions that were raised. The article by Fort et al. (2009) is a comprehensive review of the hypothalamic, brainstem and thalamocortical networks involved in generating REM sleep and non-REM sleep. The authors summarize how these systems initiate and maintain sleep, and how dysfunctional networks might cause sleep disorders. In contrast to this network-based view of sleep, Rector et al. (2009) present novel physiological insights suggesting differential sleep regulation across cortical modules and depending on use during wakefulness. Franken & Dijk (2009) review the evidence supporting the novel concept that circadian clock genes, previously thought to be exclusively involved in timing sleep, contribute to sleep regulation and vary their expression in forebrain areas under the control of wakefulness and sleep. These findings provide a possible fundamental link between sleep and cellular metabolism. Longordo et al. (2009) focus on the repercussions of sleep loss on expression and function of neurotransmitter receptors. Their main message is that insufficient sleep interferes with trafficking and properties of neurotransmitter receptors at their target sites, thereby altering neuronal excitability and synaptic plasticity. This group of articles is completed by an overview by Riemann et al. (2009) on the pathophysiological mechanisms underlying insomnia.
Three articles present therapeutic approaches used to inducing and improving sleep and sleep-related waking functions. Winsky-Sommerer (2009) addresses classical and novel drug treatment strategies that target the major inhibitory system of the brain, i.e. GABAA receptors. Landolt & Wehrle (2009) review the potential of an emerging class of drugs interacting primarily with serotonin receptors 5-HT2A/2C to improve sleep, cognition and mood. Finally, an experimental approach to nonpharmacological interference with sleep is transcranial magnetic stimulation. Massimini et al. (2009) explore how this technique could help boost the beneficial effects of sleep on learning and lead us to understand why consciousness is suspended during sleep.
Much of the inspired atmosphere and interdisciplinary nature of the symposium is captured in the final article of Vassalli & Dijk (2009). They provide a synopsis of the lively discussions amongst speakers and audience that concluded the meeting. Their article mirrors, in a colloquial and easily accessible style, the agreements and controversies between the participants, and it reviews the pros and cons of the main themes addressed at the symposium.