Abstract
24-h rhythms in physiology and behaviour are organized by a body-wide network of endogenous circadian clocks. In mammals, a central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) integrates external light information to adapt cellular clocks in all tissues and organs to the external light-dark cycle. Together, central and peripheral clocks co-regulate physiological rhythms and functions. In this review, we outline the current knowledge about the routes of communication between the environment, the main pacemakers and the downstream clocks in the body, focusing on what we currently know and what we still need to understand about the communication mechanisms by which centrally and peripherally controlled timing signals coordinate physiological functions and behaviour. We highlight recent findings that shed new light on the internal organization and function of the SCN and neuroendocrine mechanisms mediating clock-to-clock coupling. These findings have implications for our understanding of circadian network entrainment and for potential manipulations of the circadian clock system in therapeutic settings.
Highlights
Life on earth is subjected to recurrent changes in environmental conditions due to the 24-h rotation of the earth around its axis
These cell groups are located in the medial preoptic area (MPO), the sub-paraventricular area and the dorsomedial hypothalamus (DMH)
Electrophysiological experiments demonstrate that the connections of the suprachiasmatic nucleus (SCN) with neuroendocrine centres in the hypothalamus are physically separated from autonomic connections representing an independent communication route to the periphery [82,83]
Summary
Life on earth is subjected to recurrent changes in environmental conditions due to the 24-h rotation of the earth around its axis. BMAL:CLOCK initiate the expression of other genes either directly, via binding to E-box motifs in the promotor of genes e.g., Reverse-erythroblastosis virus (RevErbα/β) [29] or albumin D-element-binding protein (Dbp) [30], or indirectly via the oscillation of output genes, so called clock controlled genes (ccgs) Through these mechanisms the TTLs drive the rhythmic expression of thousands of protein-coding and -noncoding genes. The network of cellular clocks needs to process, integrate and translate environmental signals to ensure the adaptation of endogenous physiological rhythms to external time. To this goal, the body’s clocks communicate with each other. The present article will focus on what we already know and what we still need to understand about the communication of different clocks in generating coherent circadian rhythms of physiology and behaviour
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