Two-oscillator coupling in circadian clock

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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.