Our central focus is understanding how, and why, we sleep. All terrestrial mammals exhibit the same brain states during sleep as do humans, and it is clear that sleep is essential for a healthy life, as well as being essential for life itself. Yet the most fundamental questions about sleep remain unresolved. How does the brain control our need for sleep and what benefits does sleep provide? We are also interested in the actions of anaesthetic and sedative drugs, some of which appear to act by hijacking the natural sleep circuits that drive us to sleep when we are sleep deprived. We are using molecular genetics and behavioural analysis in mice to address four key research questions:
Sleep homeostasis What drives us to sleep when we are sleep deprived? The longer we do without sleep, the pressure to sleep builds inexorably until we are compelled to sleep. Of the thousands of mouse mutants that have been studied, none has been identified that does not sleep, pointing to its vital function. We are studying brain circuits that we have identified that respond to sleep deprivation and which, when reactivated, drive sleep. We are studying circuits in the cortex, mid brain and hypothalamus to try to understand how these circuits register sleep pressure and how they are able to drive sleep.
Anaesthetics and sedatives Modern clinical practice would be impossible without general anaesthetics, yet how they act in the brain to cause sedation and loss of consciousness is unknown. At the doses of these drugs that cause sedation, however, there is good evidence that some natural pathways of sleep and arousal are selectively affected. We want to identify the likely targets of sedative drugs, both in terms of the circuits they recruit, but also in terms of the cell types on which they act. Because the circuits controlling sleep and body temperature overlap, we are particularly interested in identifying targets for drugs that could cause sedation, without the unwanted side effects of hypothermia.
Why do we sleep? One of the great mysteries of neuroscience is why we spend 30% of our lives in a state of vulnerable inactivity - sleep. What are the essential benefits that it provides? We are investigating an overlap that we have discovered between circuitry that drives sleep (particularly REM sleep) and circuitry that responds to stress. It has been proposed that one of the possible reasons we need REM sleep is to mitigate the effects of stressful experiences during waking. However, the brain circuits that might explain the connection between sleep and stress have not been identified. We are investigating such circuits in the hope that this will provide one of the reasons sleep is necessary for a healthy life.
Sleep and dementia Neurological illness, and conditions that lead to dementia, are growing in our society. It has long been known that many, if not all, neurological disorders exhibit sleep disturbances at an early stage in disease progression. Many neuroscientists have proposed that the connection between sleep and neurological illness may work both ways and that poor sleep might actually cause, as well as exacerbate, the illness. We are investigating if this is true. Using novel mice model, we are investigating how beta amyloid expression in the brain affects sleep. We are also testing the idea that the principal reason we sleep is to clear the brain of toxins, such as beta amyloids, which are thought to cause Alzheimer’s disease.