Two-oscillator coupling in circadian clock

生物钟的双振荡器模型被认为是1)夜间(E)和早晨(M)振荡器，2)视交叉上核(SCN)和限制摄食计划(RF)下的食物携带振荡器(FEO)的主起搏器，以及3)SCN起搏器和甲基苯丙胺(MAP)诱导的振荡器。本研究利用显示行为昼夜节律分裂的CS小鼠，研究了E/M振荡器、FEO和MAP振荡器之间的功能关系，得到了以下结果。为了建立诱导CS小鼠行为节律“分裂”的稳定条件，对转轮笼养小鼠进行了3种改进的明暗条件(LD6：6：6：6：6h、LD9：6：3：6h和LD9：15h)。然而，在这些条件下，CS小鼠在跑轮活动节律中没有表现出分裂。这表明，恒定黑暗(DD)是诱导CS小鼠昼夜节律“分裂”的最佳条件。在给药3h的条件下，可引起CS小鼠行为节律的改变。此外，RF还改变了SCN中时钟基因(mPer1、mPer2和mBMAL1)的表达节律。这些结果表明，CS小鼠的SCN起搏器不同于大鼠和其他品系的小鼠(C57BL/6J)，是由RF携带的。在射频和射频后即刻进食过程中，行为节律未出现分裂现象，提示E/M振荡器可能与CS小鼠FEO有关。在DD条件下饮水中加入0.01%MAP后，除出现分裂节律的自由行成分外，还出现了随时间延长的自由行活动成分。MAP给药后，分离节律的M成分消失。这些结果表明，E/M振荡器与MAP振荡器之间没有关系，M振荡器可能受MAP管理的影响。

Two-oscillator model of circadian clock has been suggested to be 1) Evening (E) and Morning (M) oscillators, 2) master pacemaker in the suprachiasmatic nucleus (SCN) and food-entrainable oscillator (FEO) under restricted feeding schedule (RF), and 3) the SCN pacemaker and methamphetamine (MAP)-induced oscillator. Present study examined the functional relationship between E/M oscillators, FEO, and MAP oscillator by using CS mouse which shows 'splitting' in the circadian rhythm of behavior and obtained following results.1. To establish the stable condition which induces 'splitting' in behavioral rhythm of CS mouse, three modified light-dark conditions (LD6:6:6:6 h, LD9:6:3:6 h and LD9:15 h) were tested for the mouse housed in a running-wheel cage. However, CS mice did not show splitting in the running-wheel activity rhythm under these conditions. This indicates that constant darkness (DD) is the best condition to induce 'splitting' in the circadian rhythm of CS mouse.2. Under RF (3 h feeding) in DD, behavioral rhythm of CS mouse was entrained by RF. In addition, clock gene (mPer1, mPer2 and mBMAL1) expression rhythms in the SCN were entrained by RF. These results indicate that the SCN pacemaker of CS mouse is entrained by RF unlike that of rats and other strain of mouse (C57BL/6J). During RF and the ad lib feeding after RF, behavioral rhythm did not show 'splitting', suggesting that the E/M oscillator might be associated with FEO in the CS mouse.3. Administration of 0.01% MAP in drinking water under DD induced the activity component which freeran with lengthened period in addition to the freerunning component of split rhythm. After MAP administration, M component of split rhythm disappeared. These results suggest that there is no relationship between E/M oscillators and MAP oscillator, and that the M oscillator might be influenced by MAP administration.