Pendergast Julie S, Yamazaki Shin
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.
Physiol Behav. 2014 Apr 10;128:92-8. doi: 10.1016/j.physbeh.2014.01.021. Epub 2014 Feb 11.
The circadian rhythm of locomotor activity in mice is synchronized to environmental factors such as light and food availability. It is well-known that entrainment of the activity rhythm to the light-dark cycle is attained by the circadian pacemaker in the suprachiasmatic nucleus (SCN). Locomotor activity is also controlled by two extra-SCN oscillators; periodic food availability entrains the food-entrainable oscillator (FEO) and constant consumption of low-dose methamphetamine reveals the output of the methamphetamine-sensitive circadian oscillator (MASCO). In this study, we sought to investigate the relationship between the SCN, FEO, and MASCO by examining the combinatorial effects of light, food restriction, and/or methamphetamine on locomotor activity. To investigate coupling between the SCN and FEO, we tested whether food anticipatory activity, which is the output of the FEO, shifted coordinately with phase shifts of the light-dark cycle. We found that the phase of food anticipatory activity was phase-delayed or phase-advanced symmetrically with the respective shift of the light-dark cycle, suggesting that the FEO is strongly coupled to the SCN and the phase angle between the SCN and FEO is maintained during ad libitum feeding. To examine the effect of methamphetamine on the output of the FEO, we administered methamphetamine to mice undergoing restricted feeding and found that food-entrained activity was delayed by methamphetamine treatment. In addition, restricted feeding induced dissociation of the MASCO and SCN activity rhythms during short-term methamphetamine treatment, when these rhythms are typically integrated. In conclusion, our data suggest that the outputs of the SCN, FEO and MASCO collectively drive locomotor activity.
小鼠的运动活动昼夜节律与光照和食物供应等环境因素同步。众所周知，视交叉上核（SCN）中的昼夜节律起搏器可使活动节律与明暗周期同步。运动活动还受两个SCN外振荡器的控制；周期性的食物供应可使食物可调节振荡器（FEO）同步，而持续摄入低剂量甲基苯丙胺则可揭示甲基苯丙胺敏感昼夜振荡器（MASCO）的输出。在本研究中，我们试图通过研究光照、食物限制和/或甲基苯丙胺对运动活动的联合作用，来探究SCN、FEO和MASCO之间的关系。为了研究SCN和FEO之间的耦合，我们测试了作为FEO输出的食物预期活动是否会随着明暗周期的相位变化而协同变化。我们发现，食物预期活动的相位会随着明暗周期的相应变化而对称地出现相位延迟或提前，这表明FEO与SCN紧密耦合，且在自由进食期间SCN和FEO之间的相位角保持稳定。为了研究甲基苯丙胺对FEO输出的影响，我们给限食小鼠注射甲基苯丙胺，发现甲基苯丙胺处理会延迟食物诱导的活动。此外，在短期甲基苯丙胺处理期间，限食会导致MASCO和SCN活动节律分离，而在正常情况下这些节律是整合在一起的。总之，我们的数据表明，SCN、FEO和MASCO的输出共同驱动运动活动。
