Abstract
BackgroundDaily rhythms in mammals are programmed by a master clock in the suprachiasmatic nucleus (SCN). The SCN contains two main compartments (shell and core), but the role of each region in system-level coordination remains ill defined. Herein, we use a functional assay to investigate how downstream tissues interpret region-specific outputs by using in vivo exposure to long day photoperiods to temporally dissociate the SCN. We then analyze resulting changes in the rhythms of clocks located throughout the brain and body to examine whether they maintain phase synchrony with the SCN shell or core.ResultsNearly all of the 17 tissues examined in the brain and body maintain phase synchrony with the SCN shell, but not the SCN core, which indicates that downstream oscillators are set by cues controlled specifically by the SCN shell. Interestingly, we also found that SCN dissociation diminished the amplitude of rhythms in core clock gene and protein expression in brain tissues by 50–75 %, which suggests that light-driven changes in the functional organization of the SCN markedly influence the strength of rhythms in downstream tissues.ConclusionsOverall, our results reveal that body clocks receive time-of-day cues specifically from the SCN shell, which may be an adaptive design principle that serves to maintain system-level phase relationships in a changing environment. Further, we demonstrate that lighting conditions alter the amplitude of the molecular clock in downstream tissues, which uncovers a new form of plasticity that may contribute to seasonal changes in physiology and behavior.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-015-0157-x) contains supplementary material, which is available to authorized users.
Highlights
Rhythms in mammals are programmed by a master clock in the suprachiasmatic nucleus (SCN)
These results confirm that in vivo exposure to long day lengths dissociates the SCN shell and core, which can be used to assess the functional role of region-specific communication with downstream tissues
Because we find that arginine vasopressin (AVP) expression is arrhythmic under long days, this suggests that downstream tissues are not reset by AVP but by other signals produced by the SCN shell that remain rhythmic [36,37,38]
Summary
Rhythms in mammals are programmed by a master clock in the suprachiasmatic nucleus (SCN). Neuroanatomical studies indicate that both AVP and VIP neurons form connections with proximal targets in the brain, often projecting to the same structure [5, 12] These neuroanatomical studies provide insight into SCN efferent pathways, but it remains unclear if the outputs from SCN shell and core are redundant or functionally distinct. We develop a functional assay to identify the SCN compartment that provides time-of-day cues to downstream tissues, based on previous work demonstrating that a clock maintains a stable phase relationship with its synchronizing stimulus. Extending this logic to the entraining influence of the SCN, we can infer a functional relationship when a given tissue maintains phase synchrony with a specific SCN compartment. The strength of this approach is that it does not require direct synaptic connections, nor does it require that tissues express rhythms that are in phase with the SCN
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