The Suprachiasmatic Nucleus and the Circadian Timekee** System of the Body

Abstract

We humans are diurnal – active in the day and asleep at night. Along with this pattern of rest and activity are many other timed processes of which we are not necessarily aware. Most biological and behavioral processes must be coordinated to the right time of day for optimal efficiency. Given the importance of timing for survival of the individual and the species, it is not surprising that daily rhythms are a pervasive and ubiquitous feature of life on this planet. It is unexpected, however, that these daily rhythms are not dependent on signals from the world but are generated internally within the body by a circadian timing system (named from the Latin, circa – about, dies – a day). Circadian rhythms are produced by biological clocks that control the timing of behavioral and physiological processes. In mammals, circadian rhythms are programmed by a central clock in the brain, located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The control of circadian rhythms by this small region of the hypothalamus is one of the most dramatic examples of localized function in the brain. The SCN contains approximately 20,000 neural cells that exhibit daily rhythms in gene/protein expression, electrical activity, and metabolism. SCN neurons continue to display these rhythms even when isolated as individual cells. Thus, the mechanism of circadian timekee** is a cellular property, sustained by the molecular and genetic programs operating within the cell itself. These thousands of individual SCN clock neurons synchronize to one another so that they can form a network that provides unambiguous time-of-day signals to the rest of the brain and the body. Also, the SCN synchronizes to the environment to ensure that daily rhythms are set to 24 h, properly adjusted to the local time zone, and well matched to the changing seasons. Techniques that visualize timekee** in SCN neurons has enabled sophisticated analyses of how this network functions. Insight into the molecular bases of cellular clock has led to the realization that nearly every cell in the body is a competent circadian clock. With this understanding, we now appreciate that the SCN is not the only clock in the body but is a critical brain clock for coordinating the other tissue clocks in the brain and body. In this essay, we review the ideas and research that proved foundational to our understanding of the SCN and its role in daily timekee**. We conclude by discussing the impact of this work on current studies in basic, applied, and translational research, including topics such as cancer treatment and drug addiction.