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The Importance of Stochastic Effects for Explaining Entrainment in the Zebrafish Circadian Clock.

Heussen R, Whitmore D - Comput Math Methods Med (2015)

Bottom Line: Here we investigate how the circadian clock is entrained by external cues such as light.Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal.Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

View Article: PubMed Central - PubMed

Affiliation: CoMPLEX, UCL, Physics Building, Gower Place, London WC1E 6BT, UK.

ABSTRACT
The circadian clock plays a pivotal role in modulating physiological processes and has been implicated, either directly or indirectly, in a range of pathological states including cancer. Here we investigate how the circadian clock is entrained by external cues such as light. Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal. Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

No MeSH data available.


Related in: MedlinePlus

Stochastic simulations after light pulses. All traces show stochastic stimulations that were running freely in constant darkness before being subjected to a single light pulse at low (top) and high (bottom) intensities. The right column depicts five individual oscillators, while the left column shows the average of 1000. The results are largely in line with the experimental data. The black and white boxes at the bottom of the graph indicate lights on (white) and lights off (black). Cry1a mRNA is shown in green dotted line, Cry1a in green solid line, ClockBmal dimer in red line, Per1 mRNA in blue dotted line, and Per1 in blue solid line. Light blue dotted line shows light input/intensity.
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fig6: Stochastic simulations after light pulses. All traces show stochastic stimulations that were running freely in constant darkness before being subjected to a single light pulse at low (top) and high (bottom) intensities. The right column depicts five individual oscillators, while the left column shows the average of 1000. The results are largely in line with the experimental data. The black and white boxes at the bottom of the graph indicate lights on (white) and lights off (black). Cry1a mRNA is shown in green dotted line, Cry1a in green solid line, ClockBmal dimer in red line, Per1 mRNA in blue dotted line, and Per1 in blue solid line. Light blue dotted line shows light input/intensity.

Mentions: Having obtained the experimental data presented above, we attempted to replicate in the model simulation the effect of a variable phase response, namely that light can either advance or delay the circadian rhythm, or have no effect depending on the specific timing of light pulses, thereby resetting the clocks in asynchronous populations to a common phase (see Figure 5 for a comparison of deterministic and stochastic simulations). The experimental setup was approximated in silico; that is, 1000 stochastic oscillators were desynchronized in the absence of light and subsequently exposed to light pulses of varying intensity. The resulting traces are found in Figure 6.


The Importance of Stochastic Effects for Explaining Entrainment in the Zebrafish Circadian Clock.

Heussen R, Whitmore D - Comput Math Methods Med (2015)

Stochastic simulations after light pulses. All traces show stochastic stimulations that were running freely in constant darkness before being subjected to a single light pulse at low (top) and high (bottom) intensities. The right column depicts five individual oscillators, while the left column shows the average of 1000. The results are largely in line with the experimental data. The black and white boxes at the bottom of the graph indicate lights on (white) and lights off (black). Cry1a mRNA is shown in green dotted line, Cry1a in green solid line, ClockBmal dimer in red line, Per1 mRNA in blue dotted line, and Per1 in blue solid line. Light blue dotted line shows light input/intensity.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663325&req=5

fig6: Stochastic simulations after light pulses. All traces show stochastic stimulations that were running freely in constant darkness before being subjected to a single light pulse at low (top) and high (bottom) intensities. The right column depicts five individual oscillators, while the left column shows the average of 1000. The results are largely in line with the experimental data. The black and white boxes at the bottom of the graph indicate lights on (white) and lights off (black). Cry1a mRNA is shown in green dotted line, Cry1a in green solid line, ClockBmal dimer in red line, Per1 mRNA in blue dotted line, and Per1 in blue solid line. Light blue dotted line shows light input/intensity.
Mentions: Having obtained the experimental data presented above, we attempted to replicate in the model simulation the effect of a variable phase response, namely that light can either advance or delay the circadian rhythm, or have no effect depending on the specific timing of light pulses, thereby resetting the clocks in asynchronous populations to a common phase (see Figure 5 for a comparison of deterministic and stochastic simulations). The experimental setup was approximated in silico; that is, 1000 stochastic oscillators were desynchronized in the absence of light and subsequently exposed to light pulses of varying intensity. The resulting traces are found in Figure 6.

Bottom Line: Here we investigate how the circadian clock is entrained by external cues such as light.Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal.Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

View Article: PubMed Central - PubMed

Affiliation: CoMPLEX, UCL, Physics Building, Gower Place, London WC1E 6BT, UK.

ABSTRACT
The circadian clock plays a pivotal role in modulating physiological processes and has been implicated, either directly or indirectly, in a range of pathological states including cancer. Here we investigate how the circadian clock is entrained by external cues such as light. Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal. Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

No MeSH data available.


Related in: MedlinePlus