Circadian entrainment aftereffects in suprachiasmatic nuclei and peripheral tissues in vitro

Jul 5, 2008Brain research

Lasting changes in the body's main and peripheral clocks studied outside the body

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Abstract

The free-running period (FRP) of the suprachiasmatic nuclei (SCN) was negatively correlated with the FRP of behavioral rhythms in mPer2(Luc) knockin mice.

The study investigated how circadian rhythms in peripheral tissues are influenced by entrainment to T-cycles.
Behavioral free-running period (FRP) was measured after mice were placed in constant darkness for 3 days.
No correlation was found between the FRP of four tested peripheral oscillators and behavioral rhythm FRP.
Phase relationships between PER2::LUC in the SCN and peripheral tissues changed following T-cycle entrainment.
These findings suggest that changes in FRP may result from complex interactions rather than simple period adjustments.

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Circadian rhythms are endogenous 24-h rhythms. The suprachiasmatic nuclei (SCN) of the mammalian hypothalamus serve as the master circadian pacemaker, entraining peripheral organs which also demonstrate circadian rhythms. Entrainment to LD cycles of non-24 h duration (T-cycles) induces aftereffects on period that act to bring the intrinsic period closer to the entraining cycle. Both parametric effects, such as changes in endogenous period, and non-parametric effects of light, such as instantaneous phase shifts, act synergistically to accomplish entrainment of the SCN. It is not yet known if entrainment of peripheral oscillators similarly involves both parametric and non-parametric effects. In this study, mPer2(Luc) knockin mice were entrained to either long or short T-cycles, placed into constant darkness (DD) for 3 days to measure behavioral free-running period (FRP), and then PER2::LUC bioluminescence from SCN, spleen, esophagus, lung and thymus was measured in vitro. The FRP of SCN samples was negatively correlated with the FRP of behavioral rhythms, replicating prior results in mPer1-Luc mice. The FRP of the four peripheral oscillators tested did not correlate with behavioral rhythm FRP. Evidence that the SCN may entrain peripheral tissues by shifting phase relationships was observed, in that the phase of PER2::LUC in the SCN relative to peripheral tissues and also to the onset of behavioral activity varied between groups. Our study suggests that aftereffects on FRP may be an emergent property of the system that cannot be explained by the period changes in the system components. Further, we demonstrate that the phase relationship between the rhythm in PER2 in the SCN and these peripheral tissues is altered following T-cycle entrainment.

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Circadian entrainment aftereffects in suprachiasmatic nuclei and peripheral tissues in vitro

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