Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
PLoS One. 2011;6(8):e23895. doi: 10.1371/journal.pone.0023895. Epub 2011 Aug 19.
Several experimental studies have altered the phase relationship between photic and non-photic environmental, 24 h cycles (zeitgebers) in order to assess their role in the synchronization of circadian rhythms. To assist in the interpretation of the complex activity patterns that emerge from these "conflicting zeitgeber" protocols, we present computer simulations of coupled circadian oscillators forced by two independent zeitgebers. This circadian system configuration was first employed by Pittendrigh and Bruce (1959), to model their studies of the light and temperature entrainment of the eclosion oscillator in Drosophila. Whereas most of the recent experiments have restricted conflicting zeitgeber experiments to two experimental conditions, by comparing circadian oscillator phases under two distinct phase relationships between zeitgebers (usually 0 and 12 h), Pittendrigh and Bruce compared eclosion phase under 12 distinct phase relationships, spanning the 24 h interval. Our simulations using non-linear differential equations replicated complex non-linear phenomena, such as "phase jumps" and sudden switches in zeitgeber preferences, which had previously been difficult to interpret. Our simulations reveal that these phenomena generally arise when inter-oscillator coupling is high in relation to the zeitgeber strength. Manipulations in the structural symmetry of the model indicated that these results can be expected to apply to a wide range of system configurations. Finally, our studies recommend the use of the complete protocol employed by Pittendrigh and Bruce, because different system configurations can generate similar results when a "conflicting zeitgeber experiment" incorporates only two phase relationships between zeitgebers.
几项实验研究改变了光和非光环境 24 小时周期（授时因子）之间的相位关系，以评估它们在生物钟同步中的作用。为了帮助解释这些“冲突授时因子”方案产生的复杂活动模式，我们对受两个独立授时因子强制作用的耦合生物钟振荡器进行了计算机模拟。这种生物钟系统配置最初由 Pittendrigh 和 Bruce（1959 年）采用，用于模拟他们在果蝇羽化振荡器的光和温度驯化研究。虽然最近的大多数实验将冲突授时因子实验限制在两种实验条件下，但通过比较两种不同授时因子之间（通常为 0 和 12 小时）的生物钟振荡器相位，Pittendrigh 和 Bruce 比较了 12 种不同相位关系下的羽化相位，涵盖了 24 小时的间隔。我们使用非线性微分方程的模拟复制了复杂的非线性现象，例如“相位跳跃”和授时因子偏好的突然转变，这些现象以前很难解释。我们的模拟表明，这些现象通常出现在振荡器之间的耦合相对于授时因子强度较高时。对模型结构对称性的操纵表明，这些结果可以预期适用于广泛的系统配置。最后，我们的研究建议使用 Pittendrigh 和 Bruce 采用的完整方案，因为当“冲突授时因子实验”仅包含两个授时因子之间的相位关系时，不同的系统配置可以产生相似的结果。
