Rapid resetting of the mammalian circadian clock

The suprachiasmatic nuclei (SCN) contain the principal circadian clock gove rning overt daily rhythms of physiology and behavior. The endogenous circad ian cycle is entrained to the light/dark via direct glutamatergic retinal a fferents to the SCN. To understand the molecular basis of entrainment, it i s first necessary to define how rapidly the clock is reset by a light pulse . We used a two-pulse paradigm, in combination with cellular and behavioral analyses of SCN function, to explore the speed of resetting of the circadi an oscillator in Syrian hamster and mouse. Analysis of c-fos induction and cAMP response element-binding protein phosphorylation in the retinorecipien t SCN demonstrated that the SCN are able to resolve and respond to light pu lses presented 1 or 2 hr apart. Analysis of the phase shifts of the circadi an wheel-running activity rhythm of hamsters presented with single or doubl e pulses demonstrated that resetting of the oscillator occurred within 2 hr . This was the case for both delaying and advancing phase shifts. Examinati on of delaying shifts in the mouse showed resetting within 2 hr and in addi tion showed that resetting is not completed within 1 hr of a light pulse. T hese results establish the temporal window within which to define the prima ry molecular mechanisms of circadian resetting in the mammal.