Two-oscillator coupling in circadian clock

生物钟的双振荡模式被认为是1)晚上（E)和早晨（M)振荡，2）视交叉上核（SCN）的主起搏器和限制进食计划（RF）下的食物可携带振荡器（FEO）， 3）视交叉上核起搏器和甲基苯甲胺（MAP）诱导的振荡器。本研究利用CS小鼠对E/M振子、FEO振子和MAP振子之间的功能关系进行了研究，结果表明：1.行为的昼夜节律存在“分裂”现象。为了建立诱导CS小鼠行为节律“分裂”的稳定条件，在跑轮笼中对小鼠进行了LD6:6:6:6 6 h、LD9:6:3:6 h和LD9:15 h三种改良光暗条件的实验。然而，在这些条件下，CS小鼠在跑轮活动节律中没有出现分裂。这表明持续黑暗（DD）是诱导CS小鼠昼夜节律“分裂”的最佳条件。在DD期（饲喂3 h）射频下，射频改变CS小鼠的行为节律。此外，时钟基因（mPer1， mPer2和mBMAL1）在SCN中的表达节律被射频改变。这些结果表明，CS小鼠的SCN起搏器与大鼠和其他小鼠品系（C57BL/6J）不同，是由RF携带的。2 .在进食过程中及进食后的随机进食中，行为节律未出现“分裂”现象，提示在CS小鼠中，E/M振荡器可能与FEO有关。在DD下的饮用水中添加0.01%的MAP，除了分裂节律的自由奔跑成分外，还能诱导活动成分随时间延长而自由奔跑。MAP给药后，分裂节律M成分消失。这些结果表明，E/M振子与MAP振子之间没有关系，而M振子可能受到MAP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.