Output Pathways of the Mammalian Suprachiasmatic Nucleus: Coding Circadian Time by Transmitter Selection and Specific Targeting

Every day, we experience profound changes in our mental and physical condition as body and brain alternate between states of high activity during the waking day and rest during night-time sleep. The fundamental evolutionary adaptation to these profound daily changes in our physiological state is an endogenous 24-h clock. This biological clock enables us to prepare ourselves to these daily changes, instead of only being able to show a passive and delayed response. During the past decade, enormous progress has been made in determining possible molecular components of the biological clock. An important question remains, however, regarding how the rhythmic signal from the biological clock is spread throughout the body to control its physiology and behavior. Indeed, ultimately, the only raison d'etre for the biological clock is its output (Green 1998). In the present review, we propose that the main mechanism for the spreading time-of-day information throughout the body consists of different circadian waves of suprachiasmatic nucleus (SCN) transmitter release, directed to a restricted number of specific SCN target areas, and affecting both neuroendocrine mechanisms and the peripheral autonomic nervous system.