Dissociation between light-induced phase shift of the circadian rhythm andclock gene expression in mice lacking the pituitary adenylate cyclase activating polypeptide type 1 receptor

The circadian clock located in the suprachiasmatic nucleus (SCN) organizes autonomic and behavioral rhythms into a near 24 hr time that is adjusted da ily to the solar cycle via a direct projection from the retina, the retinoh ypothalamic tract (RHT). This neuronal pathway costores the neurotransmitte rs PACAP and glutamate, which seem to be important for light-induced resett ing of the clock. At the molecular level the clock genes mPer1 and mPer2 ar e believed to be target for the light signaling to the clock. In this study , we investigated the possible role of PACAP-type 1 receptor signaling in l ight-induced resetting of the behavioral rhythm and light-induced clock gen e expression in the SCN. Light stimulation at early night resulted in large r phase delays in PACAP-type 1 receptor-deficient mice (PAC1(-/-)) compared with wild-type mice accompanied by a marked reduction in light-induced mPe r1, mPer2, and c-fos gene expression. Light stimulation at late night induc ed mPer1 and c-fos gene expression in the SCN to the same levels in both wi ld type and PAC1(-/-) mice. However, in contrast to the phase advance seen in wild-type mice, PAC1(-/-) mice responded with phase delays after photic stimulation. These data indicate that PAC1 receptor signaling participates in the gating control of photic sensitivity of the clock and suggest that m Per1, mPer2, and c-fos are of less importance for light-induced phase shift s at night.