Limits...
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 phase and amplitude of clock gene rhythms in central tissues is influenced by photoperiod. a Double-plotted rhythms in Per2 mRNA expression were measured with qRT-PCR for the cerebellum (CB), hippocampus (HIP), olfactory bulb (OB), and septum (SEP) under LD12:12 (blue symbols) and LD20:4 (red symbols). White and black bars on the abscissa represent lighting conditions. n = 3/time-point/photoperiod. *LD12:12 versus LD20:4, LS Means Contrasts, P <0.006. Cosinor analyses of Per2 rhythms are shown in Additional file 1: Table S3. b Summary plots of photoperiod-induced changes in the phase of Per2 rhythms in central tissues. Tissues are ordered by the magnitude of the difference in peak time. Dashed vertical lines indicate the magnitude of the shift displayed by the SCN shell and SCN core in vivo, as detected with PER2 immunohistochemistry (c.f., Additional file 1: Table S4). *Significant phase shift different from 0 h, one sample t-test, P <0.05. c Amplitude of core clock gene expression is reduced in all four tissues. *Student’s t-test, P <0.05. Clock gene rhythms for all four tissues are illustrated in Additional file 1: Figure S3
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: The phase and amplitude of clock gene rhythms in central tissues is influenced by photoperiod. a Double-plotted rhythms in Per2 mRNA expression were measured with qRT-PCR for the cerebellum (CB), hippocampus (HIP), olfactory bulb (OB), and septum (SEP) under LD12:12 (blue symbols) and LD20:4 (red symbols). White and black bars on the abscissa represent lighting conditions. n = 3/time-point/photoperiod. *LD12:12 versus LD20:4, LS Means Contrasts, P <0.006. Cosinor analyses of Per2 rhythms are shown in Additional file 1: Table S3. b Summary plots of photoperiod-induced changes in the phase of Per2 rhythms in central tissues. Tissues are ordered by the magnitude of the difference in peak time. Dashed vertical lines indicate the magnitude of the shift displayed by the SCN shell and SCN core in vivo, as detected with PER2 immunohistochemistry (c.f., Additional file 1: Table S4). *Significant phase shift different from 0 h, one sample t-test, P <0.05. c Amplitude of core clock gene expression is reduced in all four tissues. *Student’s t-test, P <0.05. Clock gene rhythms for all four tissues are illustrated in Additional file 1: Figure S3

Mentions: Proximal targets in the brain receive direct projections from both SCN shell and core neurons, with tissue-specific differences in the density of innervation from each region [5]. This raises the possibility that central clocks may be distinct from peripheral tissues in that they receive time-of-day cues from each SCN region in a tissue-specific manner. Because PER2::LUC rhythms in central tissues can be reset by the culture procedure [31, 32], more traditional techniques were required to address this question. Thus, to test whether photoperiodic reorganization of the SCN influences the phase of central tissues in a manner similar to peripheral tissues, brains were collected from LD12:12 and LD20:4 mice at eight time-points spanning the circadian cycle. Cerebellum, hippocampus, olfactory bulb, and septum were collected for qRT-PCR analyses of Per2 rhythms. To assess photoperiodic changes, cosinor analyses were used to evaluate whether daily fluctuations in Per2 expression were rhythmic and to determine the center of gravity of clock gene expression patterns (Additional file 1: Table S3). Under LD12:12, each tissue displayed significant Per2 rhythms with peak expression during the dark phase (Fig. 4, Additional file 1: Table S3). Under LD20:4, none of these central tissues shifted in a manner similar to the SCN core. Rather, the cerebellum and hippocampus displayed a 3 h advance of the Per2 rhythm, while the olfactory bulb and septum did not shift significantly. Overall, these results support the conclusion that downstream oscillators are reset by time-of-day cues controlled specifically by the SCN shell, which is similar to conclusions based on PER2::LUC rhythms in peripheral tissues.Fig. 4


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 phase and amplitude of clock gene rhythms in central tissues is influenced by photoperiod. a Double-plotted rhythms in Per2 mRNA expression were measured with qRT-PCR for the cerebellum (CB), hippocampus (HIP), olfactory bulb (OB), and septum (SEP) under LD12:12 (blue symbols) and LD20:4 (red symbols). White and black bars on the abscissa represent lighting conditions. n = 3/time-point/photoperiod. *LD12:12 versus LD20:4, LS Means Contrasts, P <0.006. Cosinor analyses of Per2 rhythms are shown in Additional file 1: Table S3. b Summary plots of photoperiod-induced changes in the phase of Per2 rhythms in central tissues. Tissues are ordered by the magnitude of the difference in peak time. Dashed vertical lines indicate the magnitude of the shift displayed by the SCN shell and SCN core in vivo, as detected with PER2 immunohistochemistry (c.f., Additional file 1: Table S4). *Significant phase shift different from 0 h, one sample t-test, P <0.05. c Amplitude of core clock gene expression is reduced in all four tissues. *Student’s t-test, P <0.05. Clock gene rhythms for all four tissues are illustrated in Additional file 1: Figure S3
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: The phase and amplitude of clock gene rhythms in central tissues is influenced by photoperiod. a Double-plotted rhythms in Per2 mRNA expression were measured with qRT-PCR for the cerebellum (CB), hippocampus (HIP), olfactory bulb (OB), and septum (SEP) under LD12:12 (blue symbols) and LD20:4 (red symbols). White and black bars on the abscissa represent lighting conditions. n = 3/time-point/photoperiod. *LD12:12 versus LD20:4, LS Means Contrasts, P <0.006. Cosinor analyses of Per2 rhythms are shown in Additional file 1: Table S3. b Summary plots of photoperiod-induced changes in the phase of Per2 rhythms in central tissues. Tissues are ordered by the magnitude of the difference in peak time. Dashed vertical lines indicate the magnitude of the shift displayed by the SCN shell and SCN core in vivo, as detected with PER2 immunohistochemistry (c.f., Additional file 1: Table S4). *Significant phase shift different from 0 h, one sample t-test, P <0.05. c Amplitude of core clock gene expression is reduced in all four tissues. *Student’s t-test, P <0.05. Clock gene rhythms for all four tissues are illustrated in Additional file 1: Figure S3
Mentions: Proximal targets in the brain receive direct projections from both SCN shell and core neurons, with tissue-specific differences in the density of innervation from each region [5]. This raises the possibility that central clocks may be distinct from peripheral tissues in that they receive time-of-day cues from each SCN region in a tissue-specific manner. Because PER2::LUC rhythms in central tissues can be reset by the culture procedure [31, 32], more traditional techniques were required to address this question. Thus, to test whether photoperiodic reorganization of the SCN influences the phase of central tissues in a manner similar to peripheral tissues, brains were collected from LD12:12 and LD20:4 mice at eight time-points spanning the circadian cycle. Cerebellum, hippocampus, olfactory bulb, and septum were collected for qRT-PCR analyses of Per2 rhythms. To assess photoperiodic changes, cosinor analyses were used to evaluate whether daily fluctuations in Per2 expression were rhythmic and to determine the center of gravity of clock gene expression patterns (Additional file 1: Table S3). Under LD12:12, each tissue displayed significant Per2 rhythms with peak expression during the dark phase (Fig. 4, Additional file 1: Table S3). Under LD20:4, none of these central tissues shifted in a manner similar to the SCN core. Rather, the cerebellum and hippocampus displayed a 3 h advance of the Per2 rhythm, while the olfactory bulb and septum did not shift significantly. Overall, these results support the conclusion that downstream oscillators are reset by time-of-day cues controlled specifically by the SCN shell, which is similar to conclusions based on PER2::LUC rhythms in peripheral tissues.Fig. 4

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