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Shell neurons of the master circadian clock coordinate the phase of tissue clocks throughout the brain and body.

Evans JA, Suen TC, Callif BL, Mitchell AS, Castanon-Cervantes O, Baker KM, Kloehn I, Baba K, Teubner BJ, Ehlen JC, Paul KN, Bartness TJ, Tosini G, Leise T, Davidson AJ - BMC Biol. (2015)

Bottom Line: 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.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.Overall, 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Marquette University, Milwaukee, WI, 53233, USA. jennifer.evans@marquette.edu.

ABSTRACT

Background: Daily 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.

Results: Nearly 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.

Conclusions: Overall, 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.

No MeSH data available.


Related in: MedlinePlus

The amplitude of AVP expression in the SCN is decreased by long day photoperiods. Double-plotted rhythms of PER2 and AVP expression measured in the SCN with immunohistochemistry. White and black bars on the abscissa represent lighting conditions. n = 4–8/time-point/photoperiod. *LD12:12 versus LD20:4, LS Means Contrasts, P <0.006. Cosinor analyses of PER2 and AVP rhythms are in Additional file 1: Table S4
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Fig6: The amplitude of AVP expression in the SCN is decreased by long day photoperiods. Double-plotted rhythms of PER2 and AVP expression measured in the SCN with immunohistochemistry. White and black bars on the abscissa represent lighting conditions. n = 4–8/time-point/photoperiod. *LD12:12 versus LD20:4, LS Means Contrasts, P <0.006. Cosinor analyses of PER2 and AVP rhythms are in Additional file 1: Table S4

Mentions: The marked reduction in the amplitude of rhythms in downstream tissues may indicate that there are functionally important outputs from both SCN compartments, with the SCN shell setting the phase of downstream tissues and the SCN core influencing amplitude. On the other hand, these results may reflect that the amplitude of rhythms in the SCN shell have been diminished by long day lengths, which would not require direct communication from the SCN core to downstream tissues. To distinguish between these two hypotheses, we tested whether LD20:4 decreased the amplitude of rhythms in the SCN shell using immunohistochemistry (Additional file 1: Figure S6, and Figure S7). Consistent with previous work [21] and the PER2::LUC imaging data described above, PER2 rhythms in the SCN shell and core were similarly phased under LD12:12 but adopted different peak times under LD20:4 (Fig. 6, Additional file 1: Table S4, see also [21]). Despite the change in phase relationship, LD20:4 did not decrease the amplitude of PER2 rhythms in either the SCN shell or SCN core (Fig. 6, Additional file 1: Table S4). To test changes in the amplitude of outputs from the SCN shell, we next analyzed rhythms in AVP protein expression (Additional file 1: Figure S7), which is a major output of the SCN shell [33]. Consistent with previous work, AVP expression in the SCN was rhythmic under LD12:12 (Fig. 6, Additional file 1: Table S4). In contrast, AVP expression was not rhythmic under LD20:4, with a 50 % reduction in amplitude of expression due to higher expression during daytime and lower expression during nighttime, relative to LD12:12 (Fig. 6, Additional file 1: Table S4). This suggests that outputs from the SCN shell are attenuated under long day photoperiods, with light-driven changes in the functional organization of the SCN producing a decrease in the amplitude of AVP rhythms. Given the import of this SCN shell output, this may provide a parsimonious explanation for diminished amplitude of clock gene/protein rhythms in downstream tissues.Fig. 6


Shell neurons of the master circadian clock coordinate the phase of tissue clocks throughout the brain and body.

Evans JA, Suen TC, Callif BL, Mitchell AS, Castanon-Cervantes O, Baker KM, Kloehn I, Baba K, Teubner BJ, Ehlen JC, Paul KN, Bartness TJ, Tosini G, Leise T, Davidson AJ - BMC Biol. (2015)

The amplitude of AVP expression in the SCN is decreased by long day photoperiods. Double-plotted rhythms of PER2 and AVP expression measured in the SCN with immunohistochemistry. White and black bars on the abscissa represent lighting conditions. n = 4–8/time-point/photoperiod. *LD12:12 versus LD20:4, LS Means Contrasts, P <0.006. Cosinor analyses of PER2 and AVP rhythms are in Additional file 1: Table S4
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4489020&req=5

Fig6: The amplitude of AVP expression in the SCN is decreased by long day photoperiods. Double-plotted rhythms of PER2 and AVP expression measured in the SCN with immunohistochemistry. White and black bars on the abscissa represent lighting conditions. n = 4–8/time-point/photoperiod. *LD12:12 versus LD20:4, LS Means Contrasts, P <0.006. Cosinor analyses of PER2 and AVP rhythms are in Additional file 1: Table S4
Mentions: The marked reduction in the amplitude of rhythms in downstream tissues may indicate that there are functionally important outputs from both SCN compartments, with the SCN shell setting the phase of downstream tissues and the SCN core influencing amplitude. On the other hand, these results may reflect that the amplitude of rhythms in the SCN shell have been diminished by long day lengths, which would not require direct communication from the SCN core to downstream tissues. To distinguish between these two hypotheses, we tested whether LD20:4 decreased the amplitude of rhythms in the SCN shell using immunohistochemistry (Additional file 1: Figure S6, and Figure S7). Consistent with previous work [21] and the PER2::LUC imaging data described above, PER2 rhythms in the SCN shell and core were similarly phased under LD12:12 but adopted different peak times under LD20:4 (Fig. 6, Additional file 1: Table S4, see also [21]). Despite the change in phase relationship, LD20:4 did not decrease the amplitude of PER2 rhythms in either the SCN shell or SCN core (Fig. 6, Additional file 1: Table S4). To test changes in the amplitude of outputs from the SCN shell, we next analyzed rhythms in AVP protein expression (Additional file 1: Figure S7), which is a major output of the SCN shell [33]. Consistent with previous work, AVP expression in the SCN was rhythmic under LD12:12 (Fig. 6, Additional file 1: Table S4). In contrast, AVP expression was not rhythmic under LD20:4, with a 50 % reduction in amplitude of expression due to higher expression during daytime and lower expression during nighttime, relative to LD12:12 (Fig. 6, Additional file 1: Table S4). This suggests that outputs from the SCN shell are attenuated under long day photoperiods, with light-driven changes in the functional organization of the SCN producing a decrease in the amplitude of AVP rhythms. Given the import of this SCN shell output, this may provide a parsimonious explanation for diminished amplitude of clock gene/protein rhythms in downstream tissues.Fig. 6

Bottom Line: 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.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.Overall, 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Marquette University, Milwaukee, WI, 53233, USA. jennifer.evans@marquette.edu.

ABSTRACT

Background: Daily 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.

Results: Nearly 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.

Conclusions: Overall, 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.

No MeSH data available.


Related in: MedlinePlus