Behavioral rhythm splitting in the CS mouse is related to clock gene expression outside the suprachiasmatic nucleus

CS mice exhibit a spontaneous splitting in the circadian rhythm of locomoto r activity under constant darkness, suggesting that they contain two weakly coupled oscillators in the circadian clock system regulating locomotor act ivity rhythm. In order to clarify whether the two oscillators are located i n the suprachiasmatic nucleus (SCN), a site of the master circadian pacemak er in mammals, circadian rhythms in mRNA of mouse Period genes (mPer1, mPer 2 and mPer3) in the SCN and cerebral cortex were examined during rhythm spl itting by in situ hybridization. In the SCN, mPer1 and mPet2 showed a circa dian rhythm with a single peak in both split and unsplit mice. The rhythms of mPer1 and mPer2 were slightly phase delayed during rhythm splitting in r eference to the activity onset, but the phase relationship between the two rhythms was not changed. In the cerebral cortex, the expression of mPer1 an d mPer2 underwent the bimodal fluctuation with peaks temporally correspondi ng to split activity components. The unsplit mice showed the circadian rhyt hms with a single peak. There was no difference in the mPer3 rhythms in eit her the SCN or the cerebral cortex between the split and unsplit mice. Thes e results indicate that the circadian oscillations of mPer1, mPet2 and mPer 3 in the SCN are not related to the rhythm splitting of CS mice. The split rhythms of the CS mice are suggested to be caused by uncoupling of oscillat ors located outside the SCN from the SCN circadian pacemaker.