The suprachiasmatic nucleus and the circadian timekeeping system of the body

Abstract

Circadian rhythms evolved to provide a distinct temporal niche for each necessary function of an organism. Neither cells nor whole animals can do everything at once, nor can everything be done optimally at any particular time of day. For example, food must be sought when it is most available and when predators are fewest. All biological processes have daily rhythms that enable them to become synchronized to local environmental conditions and to coordinate physiological responses of individual cells and organs for optimal metabolic efficiency. In mammals, the timing of many daily rhythms is organized by an internal master clock in the brain. This circadian clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus, is one of the most dramatic examples of localized function in the brain. The mammalian SCN is comprised of about 20,000 cells that are functionally and phenotypically heterogeneous. Many of these cells exhibit daily rhythms in expression of clock genes and proteins and of clock-controlled genes and proteins; thus, cells are able to keep time individually and in synchrony with each other. Input to the SCN from the light-dark cycle of the environment and from behavioral and physiological cues produced by the body keeps this timekeeping system synchronized. Output signals from the SCN coordinate the timing of cells throughout the rest of the brain and the body. Advances in understanding the molecular changes that reflect cellular clock time permit assessment of the state of individual cells and of their emergent rhythmic expression. The development of techniques that allow measurement of the state of individual cells has enabled a sophisticated understanding of the master clock in the brain and how it relays temporal information to the rest of the body's oscillators. This allows the analysis of how genetic networks are related to neuronal networks and how these give rise to the emergent properties of the circadian timing system as a whole. In this chapter, we review the ideas and research that give rise to today's thinking about the SCN and, more broadly, about the circadian timekeeping system of the body. We also point to recent basic and applied work on clock function, including the impact of circadian rhythms on aging, metabolism, and cancer. To make the data and ideas livelier and more understandable, we have presented much of the information in images that parallel the written text.