The Suprachiasmatic Nucleus and the Circadian Timekeeping System of the Body
Contribution to Book
Neuroscience in the 21st Century
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 factors 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 internally organized 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 organisms. In mammals, circadian rhythms are programmed by a master 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 timekeeping is a cellular property, sustained by the molecular and genetic programs operating within the cell itself. These thousands of individual neural clocks must be synchronized to each other so that as a group they can provide unambiguous time-of-day signals to the rest of the brain and the body. Also, the SCN must be synchronized to the external 24 h environment to ensure that the brain clock itself and the downstream tissues it controls are properly adjusted to the local time zone. The development of techniques that visualize the status of the clock in individual cells has enabled sophisticated analyses of SCN function. Also, insight into the molecular bases of circadian rhythms 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 but is the master brain clock that coordinates the function of all the other clocks located in tissues throughout the brain and body. In this essay, we review the ideas and research that proved foundational to our current understanding of the SCN and its role in the daily timekeeping. 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.