Olivia Engmann (editor) - Circadian Clock in Brain Health and Disease

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The brain is a micro-cosmos of evolution. It is fantastically adaptable to environmental circumstances we never encounter in nature, such as zero gravity, mathematics and the Internet. The constant that accompanied all life on earth from day one was the 24-h rhythm of day and night, caused by the rotation of our planet. Until recently, there has been no need to adapt to altered rhythms as environmental changes such as changing day lengths do not alter the 24 h period. It is one of the brains many formidable achievements to adjust to new time zones that only a century ago we were unable to cross at a significant speed. This plasticity, or room for play and error, is intimately intertwined with other functions of our bodies, which have to be orchestrated in a circadian manner. Hence, disturbed circadian clocks in our bodies are closely associated with illnesses, including those of the brain.

In this book, the worlds leading scientists in neuroscience and biological clocks have summarized the latest findings on circadian rhythms and the brain. The first part explores the molecular basis of cellular and molecular clocks and their interaction with metabolism. The second part applies these findings to various aspects of mental health and disease.

Unfortunately, during the production of this volume, we unexpectedly lost our dear co-author Paolo Sassone-Corsi. Paolo was undoubtedly one of the brightest biologists of our time and he will be strongly missed. He once told me, one day, if things should ever take a turn for the worse, he would just disappear. Upon closer inquiry he said, he would move to one of the many small Italian islands such as Capri or Favignana. I like to imagine that this is where he is now.

As we fall asleep at night and wake up in the morning, it is tempting to feel slave to the natural world and the unceasing progression of the hours, the days, the seasons which marks the time of our lives from the day we are born to the day we die.

But we are not; we are one step ahead of the game. Circadian clocks have developed which anticipate those predictable variations of the environment and let us exploit the opportunities which come with these changes and prepare us from the dangers we may face because of them. The clock mechanisms within us are indeed ancient, but not static: they have evolved to suit increasingly complex needs. Circadian clocks in our bodies do not just control biochemical reactions within our cells; they affect our cognitive performances, our mood, our capability to fight off infections and to clear and regenerate our bodies from the wear and tear of time, and much more.

How is this complexity achieved in the brain? The first chapters of the book deal with the basic clockwork mechanisms underpinning cellular function, from gene expression to metabolic regulation of biochemical reactions and epigenetic mechanisms implicated in regulating brain function.

While a vast literature exists that illustrates the universal nature of core clock mechanisms, less is known about the importance of circadian timekeeping in conferring a diverse palette of temporal properties to different cells within tissues and organs. Our brains contain a dazzling multitude of glial and neuronal cell controlling complex behaviours. How are cell-type specific clock mechanisms contributing to brain computations responsible for daily regulation of these behaviours? In the second part of the book, the role of clock mechanisms in different neuronal cell types involved in sleep and reward systems is discussed. Are circadian clocks within non-neuronal cells also contributing to the daily orchestration of complex behaviours in the brain? The role of circadian timekeeping in astrocytes and their relevance to control daily regulation of behaviour are discussed in this section. These chapters serve to illustrate this emerging, intercellular level of circadian regulation and to address how universal intracellular clock mechanisms may be plugged in brain circuits to organise daily patterns of physiology and behaviour.