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The Journal of Neuroscience, July 1, 2001, 21(13):4883-4890

Dissociation between Light-Induced Phase Shift of the Circadian Rhythm and Clock Gene Expression in Mice Lacking the Pituitary Adenylate Cyclase Activating Polypeptide Type 1 Receptor

Jens Hannibal1, Francoise Jamen2, Harriette S. Nielsen1, Laurant Journot2, Philippe Brabet2, and Jan Fahrenkrug1

1 Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen, Denmark, and 2 Unité Propre de Recherche 9023, Centre National de la Recherche Scientifique, 34094 Montpellier Cedex 5, France

The circadian clock located in the suprachiasmatic nucleus (SCN) organizes autonomic and behavioral rhythms into a near 24 hr time that is adjusted daily to the solar cycle via a direct projection from the retina, the retinohypothalamic tract (RHT). This neuronal pathway costores the neurotransmitters PACAP and glutamate, which seem to be important for light-induced resetting of the clock. At the molecular level the clock genes mPer1 and mPer2 are 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 light-induced resetting of the behavioral rhythm and light-induced clock gene expression in the SCN. Light stimulation at early night resulted in larger phase delays in PACAP-type 1 receptor-deficient mice (PAC1-/-) compared with wild-type mice accompanied by a marked reduction in light-induced mPer1, mPer2, and c-fos gene expression. Light stimulation at late night induced mPer1 and c-fos gene expression in the SCN to the same levels in both wild 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 mPer1, mPer2, and c-fos are of less importance for light-induced phase shifts at night.

Key words: retinohypothalamic tract; suprachiasmatic nucleus; clock genes; knock-out; mouse; light entrainment

Copyright © 2001 Society for Neuroscience  0270-6474/01/21134883-08$05.00/0


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