Co-chairs Professor Russell G. Foster (University of Oxford) and Professor Joseph S. Takahashi (University of Texas Southwestern Medical Center) talk to FENS about the next Brain Conference, part of a series of high-level meetings in key areas of contemporary neuroscience, which takes place in Copenhagen on 11 - 14 October 2015.
FENS: What is special about the general format of The Brain Conferences?
RGF & JST: The Brain Conferences represent one of the few opportunities where a relatively small number of delegates attend all scientific sessions which span the key topics and themes of the scientific discipline. Lectures are given by leading experts who provide both a gentle introduction for the novice and new data for the specialist. This allows scientists from outside the field and from across the entire discipline to meet and integrate knowledge. Critically delegates have time to interact and exchange views over the several days of the meeting. As a result, discussion is not just confined to a few questions following a presentation but develops and expands across, and usually beyond, the duration of the meeting.
FENS: What do the two disciplines [sleep and circadian biology] have to learn from each other?
RGF & JST: Remarkably, the sleep and circadian communities have not talked or worked together as much as one might have expected. Sleep research arose from clinical EEG (electroencephalogram) studies on humans, whilst the circadian community has its roots in comparative animal and plant 24h (circadian) biology. As our understanding of the neuroscience of sleep and circadian biology has emerged, particularly in the past 10 to 15 years, it has become clear that studying sleep and circadian systems in isolation – as separate processes – is profoundly unhelpful. They are intimately linked and in practice difficult to untangle at a mechanistic level. With some notable exceptions, sleep researchers tend to provide a more clinical and human dimension to the discussion, whilst circadian researchers have focused upon more mechanistic and comparative questions. However, by working together there are truly exciting opportunities. Indeed, observations first made by sleep researchers on human subjects are now informing mechanistic experiments in animal models, whilst an understanding of mechanisms generated in animal models is allowing translational medicine and the development of new evidence-based therapeutic interventions for sleep and circadian rhythm disruption across the multiple clinical specialisations.
FENS: What are the most significant new findings in sleep research?
RGF & JST: Two key developments have led to a revolution in sleep research: (i) The first set of findings related to the emerging understanding of how multiple brain structures and neurotransmitter systems act together to generate this highly dynamic and complex behavioural state. Sleep is not the simple suspension of brain activity but a tightly regulated physiological behaviour that dictates the quality and nature of our conscious state; (ii) The second key development has been the empirical demonstration and recognition that appropriate sleep is required for good health and that poor sleep has major consequences ranging across poor social interaction, cognition and memory formation; abnormal metabolic and immune function; and the sustained disruption of the stress axis. Many illnesses are associated with poor sleep, yet until very recently, the additional burden of sleep disruption on health has been barely recognised and almost never treated. Good sleep is finally being accepted as a key metric of an individual’s health and quality of life.
FENS: What are the most significant new findings in circadian neurobiology?
RGF & JST: One of the great aims of neuroscience is to place behaviour into a mechanistic context, and few other branches of neurobiology have achieved such success. For example, in the past 15 years the field has developed an increasingly detailed understanding of how a cohort of key genes and their protein products can interact at a subcellular, cellular, tissue and organ level to generate patterns of 24h physiology and behaviour, and how specific polymorphisms in these genes can give rise to defined circadian phenotypes. This is the best example we have of how gene/protein interactions ultimately give rise to defined behaviours. Furthermore, by attempting to understand how light entrains the internal circadian network to the 24h day/night cycle a new, and entirely unexpected, photoreceptor system was discovered within the vertebrate eye, including humans. Such work has led to the recognition that the eye not only provides us with our sense of space but also our sense of time; and as a consequence, this knowledge has redefined the clinical diagnosis and treatment of blindness.
FENS: What are the next big questions in sleep research that you think, or hope, will be cracked in the near future?
RGF & JST: Although progress has been good, major questions remain regarding the neuroscience of sleep. For example, how does the circadian timing system at a cellular and molecular level define the appropriate time to be awake and sustain sleep?; What are the homeostatic drivers of sleep that build during wake to provide sleep pressure and the need for sleep, and then dissipate during sleep to allow the fully awake state?; How do these circadian and homeostatic drivers of sleep interact?; Why and how does the structure of sleep change so dramatically as we age and why do the patterns of sleep and wake vary so markedly between different species? In addition, although sleep is finally being recognised as a key metric of individual health across society, and that abnormal sleep is a hallmark of disease, there is little mechanistic understanding of what happens to sleep when individuals become ill or how to correct poor sleep in disease and illness.
FENS: What are the next big questions in circadian biology that you think, or hope, will be cracked in the near future?
RGF & JST: Whilst we have a broad understanding of how circadian rhythms are generated and regulated there remain multiple key questions that are being dissected by circadian researcher community, and that have a good chance of being cracked in the near future. Such questions include: What are the differences between the central circadian oscillators within the brain and those cellular oscillators found in most cells of the body, and how do these different “clocks” talk to each other to ensure a synchronised circadian network?; How do the photoreceptors within the eye that regulate the molecular clockwork specifically alter gene expression to bring about entrainment, and do non-photic cues such as exercise or feeding use the same regulatory pathways?; How do the light regulatory mechanisms of the circadian system and sleep differ?; What is the relationship between the circadian system and other key biological processes such as the cell cycle, immune and metabolic function, and information processing in the brain and particularly by the hippocampus?; Do abnormalities in the key clock genes predispose individuals to specific diseases and health vulnerabilities?; Can we develop new and more effective ways to regulate the circadian timing system to help individuals with circadian rhythm defects?